ALKYLATIQN OF PH’EN’OL WITH 2,5 «D ICHLORO-fi, SIDIMETHYLHEXANE Thesis for We Dogma OI DII. D. MICHIGAN STATE UNIVERSITY Hamid E Doddsi (fr. 1965 TH E815 LIBRARY Michigan State Univa'sity This is to certify that the thesis entitled Alkylaticn of Phenol with 2 , 5-Di CthI‘O-Q , 5-dimethylhexane presented by Harold Everett Dodds, Jr. has been accepted towards fulfillment of the requirements for Ph.D. dqpmanlCrganic Chehistry 44 @143 Mme/f Major professor Date IT‘Axu. c1 kl} H 3 )Ci (‘7 (9 O~169 4.——__.. ,1 J I": f“ .‘ o: o w"— ‘I: S..- -- _, ABSTRACT ALKYLATION OF PHENOL WITH 2,S—DICHLORO—Z,S—DIMETHYLHEXANE By Harold E. Dodds, Jr. Hart, Corbin, Wagner, and Wu (1) found that phenol reacted with S-chloro-Z-methyl-2-pentene in the absence of a Friedel-Crafts catalyst to give as products 5,5-dimethylhomochroman, l,l-dimethyl-5— tetralol, and h,h-dimethyl-6—tetralol. The formation of these prod— ucts and the results of deuterium labeling experiments were rational— ized by a mechanism which involved reaction of the primary carbon of a dimethylcyclopropylcarbonium ion with either the oxygen, or the ortho or para positions of phenol, followed by cyclization.l This homoallylic chloride is similar to 2,S-dichloro-2-methylpentane, which is a primary-tertiary dichloride. Both compounds would be eXpected to give the same products by similar mechanisms. It seemed of interest to extend this study to 2,5—dichloro—2,5— dimethylhexane, a tertiary—tertiary dichloride, to determine whether the reaction proceeds via a homoallylic-cyclopropylcarbinyl cation, or ordinary tertiary carbonium ions. Accordingly, the non—catalyzed reaction between phenol and 2,S-dithloro-Z,S-dimethylhexane was car- ried out. Eight product fractions were detected by gas chromatography. Samples of these fractions were isolated and the infrared, ultra- violet, mass, and NMR spectra for each fraction were obtained. By analyzing each of these spectra it was determined that these fractions contained the compounds 2,2—dimethy1-h-isopropylchroman (I), l,lrdi— methyl—3-isopropyl-S—indanol (II), 3,3-dimethyl-l-isopropyl—h-indanol (III), Harold E. Dodds, Jr. l,1,h,h-tetramethyl—S-tetralol (IV), l,l,h,h—tetramethyl—o—tetralol (V), h,h,6,6-tetramethyl-2,B‘diisopropyl-3,h—dihydroindano [5,6-b] pyran (VI), 2,2,6,6,9,9—hexamethy1—h-isopropyl-3,h,6,7,8,9—hexa- hydronaphtho [2,3-b] pyran (VII), h,h,6,6,9,9-hexamethy1-2-iSOpropyl- 3,h,6,7,8,9-hexahydronaphtho[2,3—b] pyran (VIII), 1,1,h,b,5,5,8,8- oetamethyi-i,2,3,h,5,6,7,8-octahydro-9-anthro1 (IX), and 1,1,h,u, 5,S,8,8—octamethyl-l,2,3,h,5,6,7,8—octahydro-9-phenanthrol (X). The sulfuric acid catalyzed reaction between phenol and 2,5- dichloro-2,S-dimethylhexane was run according to the procedure of Bruson and Kroeger (2). From this reaction were isolated fractions having identical gas chromatographic retention times to those frac- tions of the non-catalyzed reaction containing compounds I and V—X. There was no fraction detected containing compound II which Bruson and Kroeger (2) claimed was the major product of this reaction. The products from both the non-catalyzed and the sulfuric acid catalyzed reactions can be rationalized by similar mechanisms. The bis chloride first ionized to a tertiary carbonium ion and a chloride ion. The carbonium ion attacked phenol at either the oxygen, or at the ortho or para positions. The attack was followed by a second ionization and either immediate cyclization to a tetralol, or re- arrangement to a secondary carbonium ion and cyclization to either a chroman (in the case of initial attack at oxygen) or to an indanol (in the case of initial attack at one of the aromatic ring positions). In the formation of products VI—X this sequence was repeated a second time. Harold E. Dodds, Jr. The mass Spectra of several model compounds were taken. These Spectra aided the elucidation of the structure of products I—X, and in the interpretation of their mass spectra. REFERENCES ’1. Hart, H., J. L. Corbin, c. R. Wagner, and C-Y. Wu, J. Am. Chem. Soc., §§, 3267 (1963). 2. Bruson, H. A. and J. W. Kroeger, J. Am. Chem. Soc., 92, 36 (l9hO). ALKYLATION OF PHENOL WITH 2,5-DICHLORO-2,S-DIMETHYLHEXANE By . (-L Harold E‘quodds , Jr. A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHI LOSOPHY Department of Chemistry 1965 ACKNOWLEDGMENT The author wishes to eXpress his sincere appreciation to Professor Harold Hart for his encouragement and guidance throughout the course of this investigation. Appreciation is also extended to the National Institutes of Health and the National Science Foundation who provided personal financial assistance during the summer months of l96h and 1965. ii TABLE OF CONTENTS Page INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . 1 RESULTS AND DISCUSSION . . . . . . . . . . . . . . . . . . 6 Part I. General Description of the Reactions . . . . 6 Part II. Identification of the Reaction Products . . 8 A. FraCtion A O O C O O O C C O O O O O O O O 8 B. Fraction B . . . . . . . . . . . . . . . . 17 c. Fraction c . . . . . . . . . . . .-... . . 25 D. Fraction D . . . . . . . . . .'. . . . . . 26 E. Fraction E . . . . . . . . . . . . . . . . 36 F. Fraction F . . . . . . . . . . . . . . . . h3 6. Fraction 6 . . . . . . . . . . . . . . . . b9 H. Fraction H . . . . . . . . . . . . . . . . SO I. Comparison of isopropyl regions of NMR Spectra of several compounds . . . . . . . . . . 61 Part III. Mechanism of the Reaction . . . . . . . . 63 Part IV. Use of Mass Spectrometry in the Elucidation of Molecular Structures of Chromans, Indanols, and Tetralols . . . . . . . . 71 EXPERIMENTAL . . . . . . . . . . . . . . . . . . . . . . . 82 Elution chromatography, Gas chromatography, Thin- layer chromatOgraphy, Infrared Spectra . . . . . . . . . 83 Ultraviolet spectra, Mass spectra, NMR Spectra, Micro- analyses, Melting points . . . . . . . . . . . . . 8h Part I. The Alkylation Reaction . . . . . . . . . . 85 A. Preparation of 2,5—dichloro-2,5-dimethy1- hexane o o o o o o o o o o o o o o o o o 85 B. Non-catalyzed reaction of 2,5-dichloro—2,S— dimethylhexane with phenol . . . . . . . 85 C Sulfuric acid catalyzed reaction of 2 ,5- di- chloro- 2 ,S- -dimethylhexane with phenol . . 86 TABLE OF CONTENTS - Continued Part II. Product Isolation . A. Fraction A . . . B. Fraction B . . . C. Fraction C . . . D. Fraction D E. Fractions E - H Part III. Estimated Yields of Products A through the Non-catalyzed and Sulfuric Acid Catalyzed Reactions . SUMMARY . . . . . . . LITERATURE CITED . . . . . . . . iv in Page 87 87 88 88%” 91 95 98 LIST OF TABLES Page Ultraviolet spectra of several ethers . . . . . . . 9 Ultraviolet Spectra of several phenols . . . . . . . 18 Isopropyl regions of NMR Spectra of several compounds 62 Amounts of reactants . . . . . . . . . . . . . . . . 93 Estimated amounts of reactants recovered and products Ob tai ne d o o o o o o o o o o o o o o o o o o o c ‘93 FIGURE 10. 11. 12. 13. 114. 15. 1o. 17. 18. 19. 20. 21. LIST OF FIGURES Infrared Spectrum of fraction A . Ultraviolet Spectrum of fraction A Mass Spectrum of fraction A NMR spectrum of fraction A Enlargement of region containing methylene and methine hydrogens in the NMR spectrum of fraction A Infrared spectrum of fraction B Ultraviolet spectrum of fraction B Mass Spectrum of fraction B . NMR Spectrum of fraction B Infrared spectrum of fraction C . Ultraviolet Spectrum of fraction C Mass Spectrum of fraction C . NMR spectrum of fraction C Infrared spectrum of fraction D . Ultraviolet spectrum of fraction D Mass Spectrum of fraction D . NMR spectrum of fraction D Infrared Spectrum of fraction E . Ultraviolet spectrum of fraction E Mass spectrum of fraction E . NMR Spectrum of fraction E vi Page 12 13 1h 15 16 21 22 23 2h 27 28 29 3o 32 33 3h 35 39 Lo h1 h2 LIST OF FIGURES - Continued FIGURE 22. 23. 21.. 2S. 26. 27. 28. 29. 3o. 31. 32. 33. 3h. 35. 36. 37. 38. Infrared spectrum of fraction F . Ultraviolet Spectrum of fraction F . . Mass Spectrum of fraction F . . . . . NMR Spectrum of fraction F . . . . . Infrared spectrum of fraction G . . . Ultraviolet spectrum of fraction G Mass Spectrum of fraction G . NMR Spectrum of fraction G . . . Infrared Spectrum of fraction H . Ultraviolet spectrum of fraction H Mass Spectrum of fraction H . . . . . NMR Spectrum of fraction H . . . . Mass Mass Mass Mass Mass Spectrum Spectrum Spectrum Spectrum Spectrum of 1,1-dimethyl-S-tetralol of l,l-dimethy1-6-tetralol of h,h-dimethy1—6-tetralol of l,1,3-trimethy1—h-indanol of l-isopropyl-S—indanol vii O INTRODUCTION INTRODUCTION Reactive alkyl halides such as those with a tertiary, allylic, benzylic, or homoallylic group, can alkylate an activated aromatic nucleus (i.e., phenol) without the use of a Friedel—Crafts catalyst (l—S). Such compounds as t-butyl chloride (2), a—phenethyl chloride (3), triphenylmethyl chloride (h), and S—chloro-2-methyl-2-pentene (5) have reacted with phenol to evolve hydrogen chloride and have yielded nuclearly alkylated products. Bruson and Kroeger (6) used 2,5—dichloro—2,S-dimethylhexane to alkylate phenol with various Friedel-Crafts catalysts. When aluminum chloride was used as the catalyst the product isolated was l,l,h,h— tetramethyl—6-tetralol (I), m.p. th.O-1h5.2°. The structure was based on the following evidence. Oxidation with potassium perman- ganate yielded l,l,h,h—tetramethy1adipic acid (II). Like B-naphthol, the condensation of the tetralol with formaldehyde in acid solution yielded a crystalline methylene dinaphthol derivative (III), m.p. 2320. Reaction of the tetralol with chloroacetic acid gave a deriva- tive (IV), m.p. l6h-1650. , H w OOH OOH Iii) S X75 \1/ ClCH 2COOH II on HO OCHZCOOH CH2 I IV 2 II 3 When either sulfuric acid or boron trifluoride was used as the Friedel-Crafts catalyst a different phenolic product, m.p. 97-980 (6) was obtained. This compound gave an oxyacetic acid derivative, m.p. 112—1130, but did not yield a crystalline derivative with form— aldehyde nor did it yield any identifiable acid upon oxidation with permanganate. It was claimed (6) that the phenol was not 1,1,h,h- dimethyl-S-tetralol because the authors were also able to obtain two different products when 2,6-dimethylphenol was reacted with 2,5—di- chloro—2,S—dimethylhexane with different catalysts. [With an aluminum chloride catalyst they obtained a product melting at 165°, but with a sulfuric acid catalyst the product obtained distilled at 1560/6 mm.] The phenol melting at 97—980 was recovered without any rearrangement when it was heated with aluminum chloride. Since there was no re— arrangement it was concluded that this phenol did not contain an open chain. Having eliminated the possibility of an acyclic phenol and a phenol substituted in the 2 position, Bruson and Kroeger con— cluded that the phenol melting at 97-980 was probably 1,1-dimethy1- CO 0“ V 3-isopropyl-S-indanol (V). Whereas 2,5-dichloro-2,S-dimethylhexane is a tertiary-tertiary dihalide, a system analogous to a primary-tertiary dihalide was studied by Hart, Corbin, Wagner, and Wu (5). They showed that the reaction of S-chloro-2-methyl-2-pentene and phenol without a h Friedel-Crafts catalyst gave as products 5,5-dimethy1homochroman (VI), 1,1-dimethy1-5-tetra1o1 (VIII), and h,h-dimethy1—6-tetralol (VIII). ()5 (I5 VIII The formation of these products and the results of deuterium labeling eXperiments were rationalized in terms of the dimethylcyclopropyl carbonium ion (IX). The ion was formed in the following manner: We —e >———*<:\ + a- IX The products were formed by reaction of a primary site of the car- bonium ion with either the oxygen or the ortho or para positions of the phenol and subsequent cyclization. The purpose of this thesis was to study the non-catalyzed re- action between 2,S—dichloro-2,S-dimethylhexane and phenol and to determine whether it would be necessary to invoke such an ion or an intermediate, or whether the products might be accounted for via ordinary tertiary carbonium ions. When the non—catalyzed reaction between phenol and 2,5—dichloro—2,S-dimethylhexane was carried out eight product factions were detected by gas chromatography. In order to find out whether one of these eight products was the phenol melting at 97-980 reported by Bruson and Kroeger (6) the sulfuric acid catalyzed reaction between phenol and the bis chloride was also run. 5 Six product fractions were produced in this reaction which had identical retention times on the gas chromatograph to six of the eight product fractions of the non-catalyzed reaction. The struc— ture determination of all these products forms the main body of this thesis. RESULTS AND DISCUSSION RESULTS AND DISCUSSION Part I. General Description of the Reactions The non-catalyzed reaction of phenol with 2,5-dichloro-2,5- dimethylhexane was run without using a solvent. The bis chloride (0.55 mole) and a four-fold excess of phenol (2.12 moles) were heated at 85—900 for h hours at which time the evolution of hydrogen chloride had ceased. This reaction mixture was dissolved in ether and extracted with a portion of 10% aqueous potassium hydroxide and two portions of Claisen's alkali. The basic extracts were neutralized and extracted with ether. The four ether solutions were dried, filtered, concentrated, and weighed. The sulfuric acid catalyzed reaction was carried out by a pro- cedure Similar to that reported by Bruson and Kroeger (6). Equi- molar amounts of the his chloride and phenol (0.1h mole each) were added dropwise as a melt to a 79% sulfuric acid solution at 10°. After stirring the reaction mixture for 22 hours at room temperature and for 1 hour at 90°, the mixture was poured into ice-water. The aqueous mixture was extracted with ether and the combined ether ex- tracts were extracted with 10% aqueous potassium hydroxide and with Claisen's alkali. The basic extracts were neutralized and extracted with ether. The three ether solutions were dried, filtered, concen— trated, and weighed. The extracts from the non-catalyzed reaction contained eight product fractions which were detected by gas chromatography. These 7 fractions Shall henceforth be designated as fractions A—H. The ex- tracts from the sulfuric acid catalyzed reaction contained six product fractions. These Six fractions had identical retention times on the gas chromatograph to fractions A and D-H of the non-catalyzed reaction. Fractions A and E—H were found largely in the neutral extracts of both reactions. The recovered! bis chloride was found only in the neutral extract of the sulfuric acid catalyzed reaction. Recovered phenol and fractions B-D were found largely in the basic extracts of the non-catalyzed reaction. Recovered phenol and D were found largely in the basic extracts of the sulfuric acid catalyzed reac- tion. A complete separation was not effected by extraction. There— fore, smaller amounts of the neutral products were found in the basic extracts and vice versa. In addition to the recovered reactants and products A-H a considerable amount of polymer was detected in the first Claisen's alkali extract of the non-catalyzed reaction. In order to obtain samples of fractions A-C and E-H additional separations had to be made. Pure D was obtained by recrystallizing the Claisen's alkali extract of the sulfuric acid catalyzed reaction from aqueous ethanol. Fractions A, C, and E-H were obtained by elu— tion and gas chromatography. The neutral extract of the non-catalyzed reaction, when eluted on a column containing acid-washed alumina gave Several fractions. Among these were two which contained better than 90% A, a third which contained about 99% C, and another which con— tained a mixture of E-H only. The fraction containing C was recrystal- lized from petroleum ether. Pure A was collected when the enriched fractions of A were injected into a gas chromatograph. Fractions E 8 and H were collected when the fraction containing E-H only was in— jected into a gas chromatograph. Fractions F and G were obtained by eluting the neutral extract of the sulfuric acid catalyzed re— action through a column containing acid-washed alumina. The sample of B was obtained by distilling the first Claisen's alkali extract of the non-catalyzed reaction through a Spinning band column. The main product of the non-catalyzed reaction was C which was obtained in a h0.7% yield. The yields of the other products in this reaction were: A, 6.5%; B, L.2%; D, 5.1%; E, 2.7%; F, 2.0%; c, 2.9%; and H, 0.9%. The main product of the sulfuric acid catalyzed re— action was D which was obtained in a 33% yield. The yields of the other products in this reaction were: A, a trace amount; E, 0.30%; F, l.3h%; G, h.0%; and H, 0.28%. A considerable amount of both reactants was recovered from the sulfuric acid catalyzed reaction. When a sample of each fraction had been obtained the infrared, ultraviolet, mass, and NMR* spectra for each fraction were run. By the interpretation of these Spectra, the structures of the ten compounds in fractions A—H were determined. Part II. Identification of the Reaction Products A. Fraction A Fraction A had the molecular formula C14H200. Its infrared Spectrum (Figure 1) showed no bands at either 3500 cm.-1 or 3h00 cm.—1, 1 but had intense bands at both 1200 cm.-1 and llhO cm.” . The presence * ., Nuclear magnetic resonance. 9 of the latter bands and the absence of the former ones suggested that this compound was an ether. Bands at 1385 cm.“1 and 1370 cm.“1 indicated geminal dimethyl groups. The ultraviolet Spectrum of A in isooctane (Figure 2) had maxima at 286.5 mu (log 6 = 3.h8) and 279 mu (log 6 = 3.h7). Table 1 shows the ultraviolet Spectrum of A and the spectra of several model compounds. Table l. Ultraviolet Spectra of several ethers Compound (solvent) max (mu) log G Reference A (isooctane) 286.5, 279 3.h8, 3.h7 Figure 2 anisole (ethanol) 277, 270 3.15, 3.20 (7) chroman (ethanol) 279, 27h 3.21, 3.23 ’ (8) 2,2—dimethy1chroman .285, 279 2.h5, 2.22 (9) (cyclohexane) coumaran (isooctane) 290, 282, 279 3.h8, 3.h8, 3.h7 (10) The Spectrum was most consistent with a chroman and was inconsistent with either an acyclic aromatic ether or a coumaran. The mass spectrum of A (Figure 3) showed a parent peak at m/e 20b and a base peak at 161 (M-h3). The base peak represents the loss of a C3H7 fragment, probably an isopropyl group. Strong peaks at h3, hl, and 39 were probably due to an isopropyl group and to that group less two and four hydrogens, respectively. The peak at 189 (M—15) was only 1% of the base peak showing that the loss of a methyl group was a relatively more difficult occurrence. This suggested 10 that an isoprOpyl group was on a carbon alpha to an aromatic ring, and that no methyl group was similarly placed. This fragmentation phenomenon will be discussed in more detail in a later section of this thesis. The NMR Spectrum of A (Figure h), taken neat, was complex, but all twenty hydrOgenS could be accounted for. Four sharp peaks at T 9.h0, T 9.28, T 9.02, and T 8.90 represented 1.5 hydrogens each and were assigned to the six methyl hydrogens of an isopropyl group. The Splitting of the first two peaks and the last two peaks was 6.7 c.p.s.. This was due to the methine hydrogen of the isopropyl group. The different magnetic environment of the two methylS could be due to the asymmetry of the carbon atom to which the isopropyl group is attached. Two unsplit peaks at T 8.87 and T 8.61 represented 3.0 hydrogens each and were assigned to a geminal dimethyl group attached to the aliphatic ring. The different magnetic environment of these two methyl groups is similarly related to the asymmetry of the molecule. Two peaks at T 8.h9 and T 8.33 and two multiplets centered at T 7.59 and T 7.16 represented h.0 hydrogens as a unit and were due to an ABCD system which contained the methylene and methine hydrogens. The multiplet at T 2.9-3.h represented h.0 hydrogens and was due to a complex pattern of four aromatic hydrogens. Among the several structures which could be written for com- pound A structures X, XI, XII, and XIII are the most likely. 00 ll XII XIII Structures X, XI, and XII can be eliminated by the evidence presented above. Structure X does not contain an isopropyl group which was necessary to explain the NMR and mass Spectra of A. Structure XI is contrary to both the ultraviolet and NMR Spectra. The positions of the maxima in the ultraviolet spectrum are lower than those reported for coumaran, but are quite close to the posi- tions of the maxima for 2,2—dimethy1chroman. Structure XI likewise lacks the geminal dimethyl group on an aliphatic ring observed in the NMR Spectrum. Structure XII is eliminated by both the NMR and mass Spectra. The mass Spectrum which has an intense peak at 161 and a weak peak at 189 requires that the isopropyl group be alpha to the aromatic ring. If the structure were XII the peak at 189 would be much greater than 1% of the base peak. The NMR spectrum of A can best be interpreted by assuming struc- ture XIII rather than XII. This distinction can be seen in an en— largement of the region containing the methylene and methine hydrogens (Figure 5). In this ABCD system the signals for protons A and D are multiplets at T 7.16 and T 7.59, respectively. Protons B and C are represented in part by the peaks at T 8.h9 and T 8.33. Protons A-D are assigned as shown on the diagram of XIII in Figure 5. The signal Transmittance 100 80 70 50 110‘ 30' 20 10‘ 0 5000 12 2851 11000 Figure l. 3000 2000 Wavenumber Infrared Spectrum of fraction A. 1800 U1603 1155 i600 11.00 1 200 1000 800 650 100 - 60 50 -ho 30 ’20 10 -._.~ w—M «Haw—fire— 13 O Q. 1.18 x 10-4 moles/liter 3.h 3.2 1 1 2.20 2.80 Wavelength(mu) Figure 2. Ultraviolet spectrum of fraction A in isooctane. log 6 1h OWN 00m Oma 00H ompwco mmmz o: . ONH - _ n —q—_—¢~— 4 4—. ‘1 OOH d oompomow mo Esopooam mmmz .m opomfim Ow 00 on Om .sofi ..OOH ogens in 17 for D, the methine hydrogen on the iSOpropyl group, is split into 1h parts. It is split into a septet (J = 6.7 c.p.s.) by the six primary iSOprOpyl hydrogens and each of these signals is split into a doublet (JDA = 2.8 c.p.s.) by proton A. The remaining peaks in this region are due to an ABC pattern in which the signal due to proton A is also split by proton D (JAD = 3.6 c.p.s.). Since aPPo . - a normal ABC pattern without additional Splitting has 15 lines the complete interpretation of this system would be difficult. However, from inspection of this Spectrum a combination of constants can be obtained which is 1/2 (JAB + JAC) = 9.2 c.p.s. The position of the multiplet for proton A centered at T 7.16 is that which would be ° expected for a methine hydrogen alpha to a phenyl ring and would be much too low for a methine hydrogen alpha to an oxygen as would be required by structure XII. Since all of the above data are consistent with structure XIII and are inconsistent with any other structure, compound A has the formula represented by structure XIII. B. Fraction B Fraction B was shown by gas chromatography to contain about 15.5% of C and trace amounts of phenol and A. Its infrared Spectrum (Figure 6) had a sharp band at 3600 cm.-1 and a broad band at 3h00 cm.‘1. These bands indicated that the fraction was either an alcohol 1 or a phenol. There were also bands at 1385 cm.- and 1370 cm._1 due to geminal dimethyl groups. 18 The ultraviolet spectrum of B in cyclohexane (Figure 7) had max- ima at 285 mu (log E = 3.56), 279 mu (log 6 = 3.61), and 272 mu (log 6 = 3.52). These maxima were not typical either of a phenol substi- tuted in the 2 and 3 positions or of one Substituted in the 3 and h positions. These maxima suggested that B was probably a mixture of both kinds of phenols. Part of this spectrum was not due to the pres— ence of C, since the solution used in the reference cell contained the same concentration of C estimated to be in the sample cell. Table 2. lists the ultraviolet Spectra of fractions B, C, and D and some model compounds. The spectra of B and the model compounds were taken in cyclohexane. The Spectra of C and D were taken in isooctane. Table 2. Ultraviolet Spectra of several phenols Compound Xmax (mu) log 6 Reference B 285, 279, 272 3.51, 2.61, 3.52 Figure 7 c 280, 273 3.h1, 3.38 Figure 11 0 286, 278 3.3h, 3.32 Figure 15 h-indanol 277, 268 2.91, 28.3 (11a) 5-indanol 286, 282 3.h3, 3.b9 (llb) 5-tetralol 279, 272 3.1h, 3.13 (11c) 6-tetralol 288, 279 1 3.30, 3.30 (11d) The mass Spectrum of B (Figure 8) had distinctive peaks at m/e 20h (parent), 189, 161, and 1h7 (base peak). The peak at 1h? (M-57) could not be explained by a simple fragmentation of a C4H9 group from any reasonable structure which could be drawn. The origin of this 19 peak will be discussed in a later section of this thesis. The peaks at 189 (M-15) and 161 (M-AB) had relative intensities of 3.7 and 79, respectively. The peak at 189 was due to the loss of a methyl group. The peak at 161 was due to the loss of a C3H7 fragment which probably was an isopropyl group. There were also intense peaks at N3, L1, and 39 which were probably caused by the same type of fragmentation pattern postulated for the peaks at the same mass units found in the mass Spectrum of XIII. The NMR spectrum of B in carbon tetrachloride (Figure 9) was complex and no electronic integration of the several peaks was pos— sible. The spectrum had peaks at T 9.3L, T 9.23, T 9.15, T 9.11, and T 9.08 which were probably due to isopropyl hydrogens. It had peaks at T 8.97, T 8.78, and T 8.h9 which were probably due to gem- inal dimethyl groups on an aliphatic ring. Peaks at T 8.33, T 8.23, T 7.87, T 7.75, T 6.93, and T 6.83 were probably due to methylene and methine hydrogens. A sharp peak at T 8.01 which had an intensity that varied considerably in the several NMR spectra taken was due to a trace 0f acetone in the solution. Peaks at T 5.28 and T 5.20 were in the region normalb/occupied by a phenolic hydrogen. A multiplet at T 2.7-3.5 represented the aromatic hydrogens of B. The complexity of this spectrum, especially in the isopropyl and phenolic hydrogen regions, supported the evidence from the ultra— violet Spectrum that B was actually a mixture of two compounds which had nearly identical retention times on the gas chromatograph under the conditions used for the detection of the products. A series of possible structures is listed for the two compounds in fraction B. 0H 0H 0. HO O. XIV XV XVI H0 , HO OH XVII XVIII XIX Two of the above compounds must be the phenols having a molecular formula of Cl4H200 which are found in fraction B since no other reasonable structures can be drawn. Structures XIV and XV do not contain any isopropyl groups. Thus, both are inconsistent with the NMR and particularly the mass spectra of B. The infrared spectrum Showed that at least one of the components had a hydroxyl group which participated in intermolecular bonding. The ultraviolet spectrum suggested that one of these phenols was substituted in the 2 and 3 positions whereas the other was substituted in the 3 and h positions. These data Show that one of the compounds must be either XVI or XIX and the other must be either XVII or XVIII. In another section of this thesis it will be Shown that structures XVII and XIX are favored from mechanistic considerations. Structures XVII and XIX will be designated henceforth as compounds B—1 and B-2, respectively. oucmprEmcmuH 22 "3.6 \U C) O H '31 _ ~32 1.76 x 10 4 moles/liter 1 l 270 280 ' Wavelength (mu) Figure 7. Ultraviolet Spectrum of fraction B in cyclohexane .m compomnm mo Soupooam mmmz .w unamwm ompmcw\mmmz owH Qua OmH OOH Om on Ow. 23 _ :1 i=5 _.______ 4.2... .__._._ ..= . .. anew—2.31:3. ._ =fl . ._ o .hfi :0: 25 C. Fraction C Fraction C was the major product of the non-catalyzed reaction. Its infrared Spectrum (Figure 10) had a Sharp band at 3600 cm:1 and a weak band at approximately 3500 cmtl. It also had two bands at 1380 cm:1 and 1360 cmTI. The first two bands were typical for an alcohol or a phenol and the latter two were typical for geminal di- methyl groups. The ultraviolet spectrum of C in isooctane (Figure 11) had max- ima at 280 mu (109 E = 3.h1) and 273 mu (log 6 = 3.38). These maxima were typical of a phenol substituted in the 2 and 3 positions (see Table 2 on page 18). The mass spectrum of C (Figure 12) showed a parent peak at m/e 20h and a base peak at 189 (M—15). A large metastable peak at 176 was due to this transformation from mass 20h to mass 189. The peak at 161 (M—h3) was only 5% of the base peak. The low intensity of this peak suggested that there was no iSOpropyl group on the mole- cule which could be easily lost. The NMR spectrum of C (Figure 13) was easily interpreted. The peaks in this spectrum were at T 8.75 and T 8.60,each representing 6.0 hydrogens; T 8.37, representing h.0 hydrogens; T 5.58, repre- senting 1.0 hydrogen; and multiplets at T 3.75 and T 3.20, repre- senting the remaining 3.0 hydrogens. The peaks at T 8.75 and T 8.60 corresponded to twelve geminal dimethyl hydrogens; and at T 8.37 to four methylene hydrOgens; that at T 5.58 to the phenolic hydrogen; and the two multiplets corresponded to the three aromatic hydrogens. 26 Evidence for the presence of a methyl group and the absence of an isopropyl group, which was shown in the mass and NMR spectra, eliminated structures XVI-XIX as possibilities for compound C. The decision between structures XIV and XV can be made on the basis of the NMR, ultraviolet, and infrared spectra. The NMR showed that the magnetic environment of two of the methyl groups was different than that of the other two. A difference of this magnitude would be ex- pected for structure XIV, but not for structure XV. The ultraviolet Spectrum of C supported the choice of structure XIV because it Showed that C was a phenol substituted in the 2 and 3 positions. The ab- sorption due to the phenol group in the infrared Spectrum showed that there was little intermolecular hydrogen bonding. This lack of intermolecular hydrogen bonding suggested that the phenol was hindered. All of the above considerations Show that C has spectral properties consistent with structure XIV but inconsistent with structures XV- XIX. D. Fraction D Fraction D was the only phenolic product of molecular weight 20h detected among the products of the sulfuric acid catalyzed re— action. It was also found in a lesser amount among the products of the non-cataLyzed reaction. Its infrared spectrum (Figure 1h) had a sharp band at 3600 cm:1 and a shorter broad band at 3h50 cmTl. These bands were caused by an alcohol or a phenol which participated in considerable intermolecular hydrogen bonding. Bands at 1365 cm:1 and 1390 cmjl, characteristic of a geminal dimethyl group, were also present. I 28 0H -4 2.8h x 10 moles/liter - 3.L Log 6 r 3.2 ' 3.0 I I 270 280 Wavelength (mu) Figure 11. Ultraviolet Spectrum of fraction C in isooctane 29 0mm 00m omnm£fi\mmmz Owa 00H ONH .0 cowbompm mo evapoon mmmz h P 14. Azd 112a Om - .NH shaman OOH 2. 8 oo 3. mo _ ___ ..OH .IOM .8 29 0mm 00m 03 ompmcw\mmmz 00H 04H ONH OOH .o coaoomom mo Esopooaw mmmz 0w :0 Ob 2. .ma shaman Om OH Om cm on Om Ow OH Figure 13. 30 I l I I 3.75 5.58 8,37 8.do NMR spectrum of fraction C in carbon tetrachloride. 8.75 31 The ultraviolet spectrum of D in isooctane (Figure 15) had maxima at 286 mu (log 6 = 3.3a) and 278 mu (log 5 = 3.32). This Spectrum was typical of a phenol substituted in the 3 and h positions (see Table 2 on page 18). The mass Spectrum of D (Figure 16) Showed a parent peak at m/e 20h and a base peak at 189 (M—15). A metastable peak at 176 was due to the transition from mass 20h to mass 189. The peak at 189 represented the loss of a methyl group from a compound having the formula C14H200. The peak at 161 (M—h3) was only 6% of the base peak. The low intensity of this peak suggested that there was no easily lost isopropyl group on the molecule. The NMR Spectrum of compound D in acetone-d6 (Figure 17) was easily interpreted. Two peaks at T 8.77 and T 8.38 represented 12.0 and h.0 hydrogens, reSpectively; a multiplet at T 2.8-3.5 represented 3.0 hydrogens; and a peak at T 2.32 represented the remaining hydrogen. The peak at T 8.77 was due to two pairs of geminal dimethyl hydrogens; the peak at T 8.3h to four methylene hydrogens; the multiplet to the aromatic hydrogens; and the remaining peak at T 2.32 to the phenolic hydrogen. This last peak is quite low for a phenolic hydrogen. Its position was probably due to proton interchange with a trace of water in the acetbne-d6 solvent. Since all of the other NMR Spectra were rurieither neat or using carbon tetrachloride as a solvent this was the only spectrum where the peak for the phenolic hydrogen was found at such a low position. The evidence for the presence of only methyl groups shown in both the mass and NMR Spectra eliminated structures XVI-XIX as possible T 33 0H -4 1.87 x 10 moles/liter l Log 6 270 280 IWavelength (mu) 290 Figure 15. Ultraviolet Spectrum of fraction D in isooctane. 3h .. 0% CON 03 8 a. _ .Q compomnm mo Eoupooam mmmz .bH onvmwm ompmny\mmmz H 04H OmH OCH 0 OJ Om . . — a. 8 .._c_.__4 4T3§§é_a=_._§4j __. - _o , :2 .TON on 0: av ow .. ooa H0 35 I 2.32 Figure 17. IULJ‘IWJH I I I 2.8 3.5 8.38 NMR Spectrum of fraction D in acetone-d6. 36 structures for D. The decision between structures XIV and XV can be made on the basis of the NMR, ultraviolet, and infrared spectra. The NMR Spectrum showed that both sets of geminal dimethyl groups had equivalent magnetic environments. The ultraviolet spectrum was con- sistent with a phenol substituted in the 3 and h positions. The infra— red spectrum showed that there was considerable intermolecular hydro— gen bonding in a solution of D. This meant that the phenol was probably not hindered. All of the above considerations Show that compound D has Spectral properties only consistent with XV. Compound D melted at 1h2-lh3° and was probably identical to the compound melting at 1h5° reported earlier by Bruson and Kroeger (6), who showed chemically that their compound had structure XV (see Introduction). E. Fraction E Fraction E was found in small amounts in the neutral extracts of both the non-catalyzed and the sulfuric acid catalyzed reactions. Its infrared spectrum (Figure 18) had no bands in the region from 3600 cm:1 to 3h00 cmTl. There was an intense band at 1190 cm:1 and many other sharp bands in the region from 1200 cm:1 to 1050 cmjl. The lack of bands in the former region and the presence of a strong band at 1190 cm:1 suggested that compound E was an ether. Bands at 1390 cm?1 and 1370 cm?1 suggested that E had geminal dimethyl groups. The ultraviolet Spectrum of E in cyclohexane (Figure 19) had maxima at 298 mu (log 6 = 3.03), 292 mu (log 6 = 3.0h), and 288 mu (log 6 3.06). This ultraviolet'spectrum showed that E had a dif- ferent ring system than any of the previously isolated compounds. 37 The mass Spectrum of E (Figure 20) had a parent peak at m/e 31h and a base peak at 271 (M-h3). The base peak represented the facile loss of a C3H7 fragment, probably an isopropyl group. None of the other peaks were greater than 10% of the base peak except the peaks at L3 and hl which have been previously cited as probably being as- sociated with an iSOpropyl fragment. The NMR spectrum of E (Figure 21) was complex. Electronic inte- gration of part of the spectrum was possible. Peaks at T 9.h0, T 9.33, T 9.27, T 9.19, T 9.0h, and T 9.00, each representing 1.5 hydrogens, together with two peaks hidden under a peak at T 8.87 constituted the eight peaks of two isopropyl groups. The peak at T 8.87 less the two hidden peaks and peaks at T 8.82, T 8.69, and T 8.62 each represented 3.0 hydrogens. These peaks were associated with four magnetically unequivalent methyl groups which were not Split by any protons on adjacent carbons. The areas under peaks at T 8.33 and T 8.13 and multiplets centered at T 7.7 and T 7.0 could not be integrated electronically. These peaks were in the region of the Spectrum usually associated with methylene and methine hydrogens. Peaks at T 3.60 and T3.10 each represented 1.0 hydrogen. These two peaks in the region of aromatic protons Split each other by less than 1 c.p.s.. Jackman (12) stated that mutual splitting is 7-10 c.p.s. for ortho protons, 2-3 c.p.s for meta protons, and l c.p.s. for para protons. The two aromatic protons of E must therefore be para to each other. The information already presented limits consideration to struc- tures XX-XXIV. Structure XX can be eliminated immediately. The NMR 38 Spectrum of XX would not Show four separate unsplit methyl groups as are found in the NMR spectrum of E. The dxfice between the re- maining structures can be made by comparing the NMR spectrum of E 60. 600 60. é o 600 with the NMR Spectra of A and B. If the oxygen-containing aliphatic ring of B were similar to the corresponding ring in A, the NMR spectra of the two compounds would be similar in the isopropyl proton region. Since these Spectra are not similar in that region those structures which propose an oxygen-containing aliphatic ring for E similar to that in A can be eliminated. A section comparing the isopropyl region of the NMR spectra of several compounds is included later in this thesis. Part of the NMR spectrum of E in the isopropyl region is Similar to the corresponding part of the one for B. This indicates that the non-oxygen-containing aliphatic ring in E is probably similar to the aliphatic ring of B. On the basis of this evidence structure XXIV is therefore favored. The choice of XXIV rather than the other structure will be discussed in more detail in the section of the thesis covering the mechanism of these reactions. b0 ~3.0 Log 6 ”2.8 1—2.6 6.88 x 10-4 moles/liter I I j 260 280 300 Wavelength (mu. Figure 19. Ultraviolet Spectrum of fraction E in cyclohexane 100- 80‘ 70~ 30' 20' 20 Figure 20. £10 Mass Spe 400 >80 '70 F60 .50 '110 .30 ~20 ' 10 FigL b3 F. Fraction F Fraction F was found chiefly in the neutral extracts of both the non-catalyzed and the sulfuric acid catalyzed reactions. Trace amounts were also found in the second Claisen's alkali extract of the non-catalyzed reaction. The infrared Spectrum of F (Figure 22) had no bands in the region from 3600 cm._1 to 3h00 cm.-1 and it had two intense bands at 1200 cm.-1 and llh0 cm.-1. The absence of bands in the 3600 cm.-1 to 3h00 cm.-l region and the presence of the two intense bands indicated that F was an ether. Strong bands at 1385 cm.‘1 and 1370 c.-1 were due to the presence of geminal dimethyl groups. The ultraviolet spectrum of F in isooctane (Figure 23) had maxima at 293 mu (log E = 3.55) and 28h mu (log 6 = 3.51). This Spectrum was not Similar to any of the previously mentioned spectra and there- fore must have been due to a different ring system. The mass Spectrum of F (Figure 2h) had a parent peak at m/h 31h and a base peak at 271 (M-h3) which was due to the loss of a C3H7 fragment, probably an isopropyl group. A peak at 299 had an intensity of 65% of the base peak and was due to the loss of a methyl group. There were strong peaks at L3, LI, and 39 which are generally associ- ated with a strong M-h3 peak. There was a peak at h5 which had an intensity of 19.2% of the base peak. An attempt to rationalize the existence of this peak will be made in a later part of this thesis. The NMR Spectrum of F in carbon tetrachloride (Figure 25) was complex, but electronic integration of part of the spectrum was pos— sible. Four peaks at T 9.38, T 9.25, T 9.00, and T 8.87, repre— senting 1.5 hydrogens each, were assigned to an isopropyl group. bu Peaks at T 8.80, T 8.73, and T 8.62 represented 3, l2, and 3 protons, respectively. The two smaller peaks represented a geminal dimethyl group on the ring containing the isopropyl group. The Single peak at T 8.73 was due to the four methyl groups on the other ring. The peak at T 8.33 was due to four methylene hydrogens. The remaining peaks in that region represented part of the ABCD system composed of the methylene and methine hydrogens in the ring containing the iso- propyl group. Peaks at T 3.27 and T 2.80 were due to aromatic hydro- gens. These two protons must have been para to each other since they split each other by less than 1.0 c.p.s. (12). There are two possible structures which are reasonable for F. The choice between XXV and XXVI can be made by comparing the NMR Spectra of compounds A and F. A comparison of these two spectra in the iSOpropyl and geminal dimethyl regions showed that part of this region for the spectrum of F was superimposable on the spectrum of A. Compound F must have therefore the,same structure as A in the ring containing the isopropyl group. According to this evidence structure XXVI is correct for compound F. A6 Log 6 "4 1 3.0 2.79 x lo moles/liter Figure 23. J 270 280 290 Wavelength (mu) Ultraviolet Spectrum of fraction F in isooctane. 1106 L 100T 70‘ 60“ 110* 30‘ 20- 20 ho Figure 2h. Mass Spectrum 0 A8 2.80- 3.27 8.33 8.73 8.87 9.25 9.00 9.38 Figure 25. NMR Spectrum of fraction F in carbon tetrachloride. 1P‘. . All «as; ..I 1.r.. V. a: . a QC vflu _ - ‘ ‘¢ 4 in a a Do ..I~ 5.. a . Cu 2.. A9 G. Fraction G Fraction G was found in the neutral extracts of both the non- catalyzed and the sulfuric acid catalyzed reactions. A small amount of G was also found in the second Claisen's alkali extract of the non-catalyzed reaction. The infrared Spectrum of G (Figure 26) had no bands from 3600 cm.-1 to 3A00 cm.-1. The absence of any bands in this region and the presence of a moderately strong band at 1185 cm.-1 indicated that this compound was an ether. The presence of strong bands at 1385 cm.-1 and 1365 cm.—1 indicated that G had geminal dimethyl groups. The ultraviolet Spectrum of G in isooctane (Figure 27) had maxima at 291 mu (log E = 3.A6) and 282 mu (log 6 = 3.AA). This was similar to the ultraviolet Spectrum of F and indicated that products F and G probably had similar ring systems. The mass Spectrum of G (Figure 28) showed a parent peak at m/e 31A and a base peak at 271 (M-A3) which was due to the loss of a 03H7 fragment, probably an isopropyl group. A large peak at 299 (M-15) had an intensity of 61.5% of the base peak. This was due to the loss of a methyl group. Large peaks at A3, A1, and 39 were present as in the other cases when there was a strong M-A3 peak. The strong peaks at 69 and 55 will be discussed in a later section of this thesis. The NMR Spectrum of G (Figure 29) was complex. Electronic integration of part of the Spectrum was possible. Four peaks at T 9.0A, T 9.01, T 8.9A, and T 8.91, each representing 1.5 hydrogens, were assigned to an iSOpropyl group. Peaks at T 8.80, T 8.75, and 50 T 8.70 were assigned to Six unsplit methyl groups. Two of these methyl groups had a magnetic environment slightly different from each other and different from the other four. The peak at T 8.37 was assigned to four methylene hydrogens. The other peaks in that region were assigned to part of an ABCD system. The two remaining peaks a T 3.A7 and T 3.02 each represented 1.0 protons. These two peaks, which were due to aromatic hydrogens, Showed a mutual Split— ting of less than 1.0 c.p.s.. These were therefore two hydrogens in the para positions on an aromatic ring (12). The only reasonable structures which can be drawn for this compound are structures XXV and XXVI. Since compound F has already been assigned structure XXVI and compounds F and G are different compounds, then compound G must have structure XXV. A comparison of the isopropyl regions of the NMR spectra of compounds E and G showed that the peaks due to the isopropyl hydrogens in the Spectrum for G can be superimposed on one of the two sets of isopropyl hydro- gens in the Spectrum for E. This means that compounds E and G must have Similar structures in the oxygen-containing aliphatic ring. This comparison serves as additional evidence for the cor- rect assignment of structures for both compounds E and G. H. Fraction H Fraction H was found in small amounts in the neutral extracts of both the non—catalyzed and the sulfuric acid catalyzed reactions. A trace amount was present in the second Claisen's alkali extract of the non-catalyzed reaction. The infrared Spectrum of H (Figure 30) AIL 7:627; ENEWZSHLF Transmittance 100 51 ms: 80' A0‘ 30‘ 20' 10- .03 V 5000 A060 Figure 26. 300'0 2000 Wavenumber Infrared Spectrum of fraction G. 1800 52 Log 6 '4 1.A9 x 10 moles/liter I I l 270 280 290 Wavelength (mu) Figure 27. Ultraviolet spectrum bf fraction G in isooctane. 5A T. spectrum of fraction G in carbon tetrachloride. \ o I. J L.) L _ — J (5 k.) a] LL 12' 55 had a sharp band at 3650 cm.-1 and no band at 3A00 cm.-l. This indicated that the fraction contained an alcohol or a phenol which was unable to participate in intermolecular hydrogen bonding. A medium strength sharp band at 1650 cm.-1 was probably due to a keto group, perhaps belonging to a minor impurity in fraction H. Bands 1 and 1365 cm.-1 were probably due to geminal dimethyl at 1395 cm.‘ groups. The ultraviolet Spectrum of H in cyclohexane (Figure 31) had maxima at 298 mu (log 6 = 2.86), 275 mu (log E = 3.5AL and 269 mu (log 6 = 3.51). This Spectrum was different than any of the spectra for the other compounds isolated from these reactions and must be- long to a different ring system. The mass Spectrum of H (Figure 32) had a parent peak at m/e 31A and a base peak at 271 (M—A3) which was due to the loss of a CSHT fragment. There were peaks at 299 (M—15) and 328 (M+1A) which had intensities relative to the base peak of 28.9% and 2.1%, respectively. The former peak was due to the loss of a methyl group and the latter one to an impourity which probably had a molecular weight of 328. Strong peaks at A3, A1, and 39 which are normally present when there is an intense M-A3 peak were also found in this spectrum. The NMR Spectrum of H (Figure 33) showed splitting only in the methylene region where it was poorly defined. The peaks in the ,aliphatic region at T 8.77, T 8.7A, T 8.59, T 8.53, and T 8.A0 had relative intensities of 9, 6, 9, 2, and 8, respectively. The first four peaks were all due to geminal dimethyl groups. The peak at T 8.A0 was broad and was due to all of the methylene hydrogens. 56 Two peaks at T 5.10 and T 3.23 were barely observable above the noise level of the Spectrum. The former peak was assigned to a phenolic hydrogen and the latter one to an aromatic hydrogen. The compound or compounds in fraction H must have either structure XXVII or XXVIII, or there must be a mixture of both structures. The NMR spectrum of H can best be explained by assuming that H is a mixture of these compounds in a ratio of 70 to 30, with XXVII as the major component. The peaks at T 8.77 and T 8.59 would be due to XXVII and those at T 8.7A and T 8.53 would be due to XXVIII. The last peak in each set would be due to the geminal 0H [lliillllll| llll Iii 0H XXVII XXVIII dimethyl groups closest to the hydroxyl group. The first peak in each set would be due to the remaining geminal dimethyl groups. Compounds XXVII and XXVIII will henceforth be designated as com- pounds H-1 and H-2, reSpectively. The ketonic impurity observed in both the infrared and mass Spectra of fraction H probably was a compound having either struc— ture XXIX or XXX. These two compounds are quinones which would come from the oxidation of H—1 and H-2. II 58 1.93 x 10'4 moles/liter ! 1 260 280 Wavelength (mu) Figure 31. Ultraviolet Spectrum of fraction H in cyclohexane. Log 6 100- 80' 70‘ 501 A0“ 30 20* 10‘ 20 Figure 32. l lllll -100 . 70 A0 Mass Spectrum 60 WWW . I 3.23 5,10 8.AO 8.53 8.97 Figure 33. NMR spectrum of fraction H in carbon tetrachloride. 61 XXIX XXX 1. Comparison of isopropyl regions of NMR spectra of several comounds The primary hydrogens of an isopropyl group in an aliphatic ring gave a distinct NMR pattern which depended on the type of ring and the position of the isopropyl group on that ring. The Spectra in this region of compounds XIII, XVII, XIX, XXIV, XXV, and XXVI from this thesis and 1,l-dimethyl—A—isopropyltetralin (XXXI), pre- pared by Barclay, Ginn, and Milligan (13), are shown in Table 3. In this table all peak positions are Shown in T units. The origin of the quartet in this region is due to two factors. If the isopropyl group is in an asymmetric molecule the two methyl groups in the isopropyl group will be in different magnetic environ— ments. The signals for each of these methyl groups will be Split in two by approximately 6.7 c.p.s. by the methine hydrogen of the isopropyl group. Whereas the Splitting by the methine hydrogen tends to be constant, the difference in magnetic environment of each methyl group varies considerably from compound to compound. In the cases presented in Table 3, type I Shows little difference in environment, but type II shows considerable difference. The difference in mag— netic environment of types III and IV comes between these two extremes. 62 Table 3. Isopropyl regions of NMR spectra of Several compounds Compound Type I Type II Type III Type IV XIII 9;A0, 9.28, 9.02, 8.90 XVII and XIX 9.3A, 9.23, (mixture) 9.15, 9.11, 9.08* XXIV 9.0A, %* 9.A0, 9.27, 9.00 (8'87) 9.33, 9.19 XXV 9.0A, 8.9A, 9.01, 8.91 XXVI 9.38, 9.25, 9.00, 8.87 XXXI 9.31, 9.19, 9.03, 8.93 *These are the positions of the five distinguishable peaks in this region which probably contains eight peaks. **This is the position of a large peak which hid the two peaks re- quired to complete this quartet. :: S: C H0 :g: ; H XIII XVII XIX too too of: XXVI XXXI 63 The closeness of the positions of the peaks within each type permits easy determination of the position of an isopropyl group by examination of a NMR spectrum. Part III. Mechanism of the Reaction The eight product fractions detected from the non-catalyzed re- action between 2,5-dichloro—2,5-dimethy1hexane and phenol contained ten compounds. These were 2,2-dimethy1-A-isopropylchroman (XIII), 1,1,A,A- tetramethy1-5-tetralol (XIV), l,1,A,A-tetramethyl-6-tetralol (XV), l,l-dimethyl-3—isopropy1-5—indanol (XVII), 3,3-dimethy1-l-isopropyl—A— indanol (XIX), A,A,6,6—tetramethy1—2,8—diisopropyl-3,A—dihydroindano [5,6-b]pyran (XXIV), A,A,6,6,9,9-hexamethy1-2—isopropyl—3,A,6,7,8,9— hexahydronaphtho[2,3-b]pyran (XXV), 2,2,6,6,9,9—hexamethyl-A—iso- propyl-3,A,6,7,8,9-hexahydronaphtho[2,3-b]pyran (XXVI), 1,1,A,A,5,5, 8,8-octamethy1-l,2,3,A,5,6,7,8-octahydro-9-anthrol (XXVII), and 1,l,A,A,5,5,8,8-octamethyl-l,2,3,A,5,6,7,8-octahydro-9-phenanthrol (XXVIII). The six product fractions detected in the sulfuric acid catalyzed reaction had identical retention times on the gas chromatograph to those fractions of the non-catalyzed reaction containing compounds XIII, XV, and XXIV-XXVII. However, XVII, which would correspond to the product previously isolated by Bruson and Kroeger (see Introduction), was not detected. Compounds XIII-XV, XVII, and XIX had molecular formulas C14H200 and were formed by the cyclialkylation of phenol by the his chloride. Compounds XXIV—XXVIII had molecular formulas C22H340 and were formed by the second cyclialkylation of one of the C14H200 products by the 6A 8 XIII XXVI NC 6.5% NC 2.0% SA trace SA 1.3A% HO OH 3’ XV XXV NC 5.1% .NC 2.9% SA 33% SA A.0 0H + ——> ——> OH X X XIV XXVIII 4 NC 0.9% C1 C1 Nc A0.7% SA 0.18% SA none I I; :: H :: mx “1 xmml NC A.2% I SA none I X XXIV NC 2.7% SA 0.30% 65 bis chloride. A scheme of all the products gives the C14H200 product from which each of the C22H340 products could be made. Included in this Scheme are the relative yields of all the products from both reactions. Since the formation of the C22H340 products can be eXplained by a two step process in which a C14H200 product is formed followed by a cyclialkylation of this product similar to the cyclialkylation of phenol, it is only necessary to describe the reaction mechanism for the formation of the C14H200 products. The reaction products can be rationalized in terms of a carbonium ion mechanism. It can be ex- plained without invoking a non-classical carbonium ion species such as that postulated by Hart, Corbin, Wagner, and Wu in a Similar re- action (See Introduction). In the first step, the bis chloride prob- ably dissociates into a tertiary carbonium ion and a chloride ion. (2&6! 9 (,4 U+ + 62— ThiS carbonium ion could react with the phenol at either the oxygen, or at the ortho or para positions. This step would be followed by the formation of a second carbonium ion which in turn would attack the same aromatic ring or another phenol molecule. All of the frac- tions isolated were due to this second attack being intramolecular; however, a considerable amount of polymer (27% of total product weight) obtained from the non-catalyzed reaction was probably due to this Second step being intermolecular. 66 Compounds XIV and XV were produced by attack of the tertiary carbonium ion of the bis chloride at the ortho and para positions of phenol, respectively. Initial attack was followed by the forma- tion of a second tertiary carbonium ion which then cyclized to a tetralol. This sequence of events is shown for the formation of XIV. OH H XIV This is a familiar type of cyclialkylation for which there are many cases cited in the literature (1A). Bruson and Kroeger (6) used 2,5-dichloro-2,5-dimethy1hexane with phenol in the presence of aluminum chloride to produce 1,1,A,A-tetramethy1—6-tetralol. Reppe and co-workers (15) used 1,A-dichlorobutane with benzene in the presence of aluminum chloride to produce a mixture containing tetra- lin, octahydroanthracene, octahydrophenanthrene, and dodecahydro— triphenylene. XIII probably was formed by attack of the tertiary carbonium ion of the his chloride on the phenolic oxygen. A second ionization, followed by rearrangement to a secondary carbonium ion and cyclization leads to the product. WI (Tho—Ls XIII 67 Hydride Shifts of this type, even though they involve conversion of a tertiary to a secondary carbonium ion, are quite common in cyclialkylations, probably because they lead to six— rather than Sevenémembered rings. For example, Barclay, Ginn, and Milligan (13) found that the reaction of l,l,A,A—tetramethy1tetralin with 2,6—di- chloro-2,6-dimethy1heptane in the presence of aluminum chloride yielded a mixture of XXXII and XXXIII. + £2 .00 N Cl. C”: XXXII XXXIII Hart, Corbin, Wagner, and Wu (5) found that the non-catalyzed addition of 5-chloro—2-methy1-2-pentenetoTimmol gneffi5-dhnflndhomoduo— IWHIaSIhBTBUUElpFOduct. This reaCtion was an exception to the rule that cyclization to a seven—membered ring is not usually favored. In this case, the reaction proceeds via the dimethylcyclopropylcar- bonium ion (see Introduction). 0H cl - O ©+Wa 0 Hart and Corbin (16) used several Friedel-Crafts catalysts for the attempted synthesis of l,l,A,A—tetramethy1—6,7-benzocycloheptene (XXXIV) from 2,5,5-trimethy1-7-phenyl—2—heptene. With aluminum 68 chloride at 0° the only product isolated was 3,3—dimethyl-l-iso- prOpyltetralin (XXXV). With boron trifluoride at 0° or with ferric chloride a mixture of products was obtained containing 33% XXXIV and 67% XXXV. There was no product obtained when stannic chloride was used as the catalyst. This study showed that ring closure to a seven-membered ring occurred only under the mildest Friedel- Crafts conditions. WT‘Q? XXXIV XXXV Compounds XVII and XIX would be formed by a process similar to the mechanism cited for the formation of XIII. In this case initial attack would be at an ortho or para position of phenol. This Sequence for the formation of XVII is Shown below. H OH —} 0H ‘4_ 0 <3)”er o XVII Whereas the determination of the structure of the two compo— nents in fraction B could not be made on the basis of Spectral evidence alone, it should now be clear that formation of structures XVII and XIX can easily be explained by the above mechanism. In order for one of the two components to be either structure XVI or XVIII, one of two less favored reaction paths would have to be 69 followed. Attack of the tertiary carbonium ion at the meta position of phenol followed by a hydride shift and cyclization would produce a mixture of XVI and XVIII. An even poorer path would involve rear- 0H 0H 0H XVI. —> —> + + + H0 XVIII rangement of the first-formed tertiary carbonium ion prior to the attack on the aromatic ring. This path would be considered poorer because it requires that the attack of the carbonium ion be the slow step. According to the reaction Scheme carbonium ion rearrangements can occur only during the slow step of the reaction. Attack of the carbonium ion at an electron rich position of phenol should be the fast step of this reaction. This sequence is given for the forma- tion of XVI. OH OH +_§ . XVI 70 Similar mechanistic considerations explain why structure XXIV was favored over structure XXIII when deciding which was correct for E. Barclay, Gray, and Milligan (17) found that l,l,A,A,5,5,8,8—octa- methyl-l,2,3,A,5,6,7,8-octahydroanthracene rearranged in the presence of aluminum chloride to give XXXVI. They suggested that this rear— rangement proceeded through a benzenonium ion intermediate. XXXVI The non-catalyzed reaction reported in this thesis could not have had a benzenonium ion intermediate because its formation requires the loss of a hydride ion. Since there is no Species in the reaction mixture capable of transferring a hydride ion Such an intermediate would be prevented from forming. In a later paper, Barclay, Ginn, and Milligan (13) suggested that the reaction of l,1,A,A-tetramethy1tetralin with 2,6-dichloro- 2,6-dimethy1heptane in the presence of aluminum chloride went through a mechanism similar to the one proposed in this thesis. ____;> *’ ___;3> products 71 It is difficult to explain why production of the 5—tetralol is favored by the non—catalyzed reaction whereas the 6—tetralol is favored by the sulfuric acid catalyzed reaction. In fact, no pro— ducts formed by initial attack at the ortho position of phenol in the sulfuric acid catalyzed reaction were even detected. Further experiments would be necessary to discover the true cause or causes of this preference. The absence of the 5—tetralol (XIV) among the products detected was not due to formation of the 5-tetralol (XIV) followed by rearrangement to the 6-tetralol (XV) under reaction conditions, Since no rearrangement occurred when a mixture of XIV in 79% sulfuric acid was heated on a steam bath for 30 minutes. Likewise, there was no XVII even detected in the products of the sulfuric acid catalyzed reaction although the presence of a small amount of XXIV suggests that some XVII could have been present at some time during the reaction. Further experiments would be required to discover what conditions if any favored the formation of an indanol (XVII) over a tetralol (XV). Part IV. Use of Mass Spectrometry in the Elucidation of Molecular Structures of Chromans, Indanols, and Tetralols Mass Spectrometry has been used extensively to elucidate the structures of complex molecules. Two excellent books which describe this technique have recently been written hy Biemann (l8) and Budz- ikiewicz, Djerassi, and Williams (19). In order to use mass Spectrometry to elucidate the structures of the compounds isolated from the reaction of phenol with 2,5-dichloro- 2,5-dimethy1hexane, the mass Spectra of several reference compounds 72 were run. These compounds are 1,1-dimethy1-5-tetralol (XXXVII), 1,1- dimethyl-6-tetralol (XXXVIII), A,A-dimethy1-6-tetralol (XXXIX), 1,1,3-trimethyl-A—indanol (XL), and l-isopropyl-S-indanol (XLI), all prepared by Corbin (20). H0 H0 XXXVII XXXVIII XXIX illl |I H0 ll' 0H XL XLI A comparison of the mass Spectra of compounds XXXVII, XXXVIII, and XXXIX shows that there is little difference between them. Since these compounds differed only in the position of the hydroxyl group on the aromatic ring, one concludes that this variation of structure between compounds does not seem to have a large effect on their mass Spectra. These data indicate that mass Specrometry probably would not be useful in distinguishing between structures XVI-XIX. A similar effect was observed by Biemann (18a), who showed that there was little difference between the mass Spectra of the three ethyl— toluenes. A much greater difference between the mass Spectra of compounds XIV and XV was observed. The origin of some of these peaks will be discussed later. 73 .AHH>xxxv Hoamoooo-m-fiarooaao-a.a no sooooono non: .am shaman omnmnm\mmmz cma ocH 04H oNH ooa cw cc on 6m . p - _ q I , 4:1 .P . :44 424% .— 11 b a a = i... 4.1—. n 4 m 1 _ _ —. —_ u. _. mo OH cm Om OS om 06 OS Ow OOH 7A Oma 02 oi .AHHH>xxxV HonnpopubuflxbpoempunH mo Esopooam mmmz omomc&\mmmz ONH OOH Ow 00 0: ON L. F .mm mommwm .____ .___i___ ___. .. ____ .. ..___a_ .d ___— : q ___ OI TOH TON .Om . or .AxHxxxV Hofimnbopubuaxnboamouanq mo aoopooom mmmz .bm whomam omomzt\mmmz Owfl 00H 04H OmH OOH Ow Ob Om p p p — _ . p . . 6.4 .. ... :fi. 4::. .;_4 fie. w —— . :11 __4_ ___ =_ :— 75 TON -0m .0: .0m .05 TO® . Om . OOH .Aaxg Hocmpcwuquflznpoawnpumafl«H mo Esopooam mmmz .Sm shaman omum£&\mmmz 76 b > IF b ..=. .31: p . .1- :— _—«.— m. q 1—— — .- owfl OOH 04H OwH OOH Om 00 0: ON PI dd— d dc ___—q- ___ OOH 77 Oma 00H 04H AHAXV Hocmpcmumuflzoonoomaufi mo adupooam mmmz .wm madman omomn&\mmmz ONH OOH 00 O b .- 1:. is _r___ ___: _. @w = _. : :2. . a - in ___ __ OI ._. -OH TON .Om 78 In all the mass spectra studied, the molecular weight was easily obtained because the parent peak due to the molecular ion generally had an intensity of 10—20% of that of the base peak. The origin of the base peak, the most intense peak due to the fragmentation of the compound, was important to the interpretation of the Spectra studied. In the spectra of model compounds XXXVII-XLI, the base peak was due to the loss of an alkyl group from a carbon alpha to the aromatic ring. This type of fragmentation probably explains the source of the base peaks in compounds XIII-XV, XXIV, and XXVI. Both Biemann (182) and Budzikiewicz, Djerassi, and Williams (19a) cite examples where this type of fragmentation is the source of the base peaks. The origin of the base peak in the Spectra of compounds XVII, XIX, XXVII, and XXVIII is due to a closely related type of frag- mentation, which may be considered a three step process. For example, in the case of XVII this fragmentation would result from the break- ing of the aliphatic ring bond of the carbon alpha to the aromatic ring, hydrogen atom transfer, and cleavage of E-butyl radical from the aromatic ring. .. 1 I + H0 —_> ITO/.232; 9mg“ L ' ' A m/e = 1A7 79 A Similar fragmentation pattern would be responsible for the base peaks of XIX, XXVII, and XXVIII. In fact, this type of fragmentation explains the origin of several peaks in the mass spectra Shown in this thesis. This type of fragmentation is probably responsible for the peak at m/e 1A7 in the mass spectrum of XIV. The base peak in the mass Spectrum of XXV is probably due to the loss of an isopropyl group from a carbon attached to oxygen. This type of fragmentation was shown by McLafferty (21) in the mass spectrum of ethyl SEE-butyl ether. Several of the peaks observed in this spectrum were due to the loss of alkyl groups from a carbon attached to oxygen. However, the base,peak in the mass Spectrum of ethyl SEE—butyl ether was not due to such a fragment, but rather to a fragment with m/e A5 for which McLafferty (21) gave the formula C2H50. Since the peak at A5 was also the base peak in the mass Spectra of methyl n-propyl ether, methyl n-butyl'ether, methyl lig— butyl ether, and diisopropyl ether he concluded that this carbonium ion was the result of alpha and beta cleavage with hydrogen rear— rangement. In the mass Spectrum of XXVI there was a strong peak at A5 (19.2%) which probably also had a Similar origin. In the mass CH 3CH=6H é m/e = A5 80 Spectrum of XIII there was a peak at m/e A5 (9.0%) which probably had the same origin as the corresponding peak for XXVI. The peaks at m/e 55 and 69 in the mass spectrum of XXV could possibly have had the following origins: «it + H.__€> CH=C(CH3)2 m/e = 55 + T———;> CH2=CHC(CH3)2 ' m/e = 69 Certain artifacts which do not have anything to do with the fragmentation pattern of the compound being examined often appear 'in mass Spectra. The causes of these artifacts are usually air, water, and mercury. Peaks due to mercury are found at 20A, 202, 201, 200, 199, and 198. Air peaks are found at A0, 32, 28, 16, and 1A. Peaks at 18 and 17 are often due to a trace of water in the system. The inclusion of small amounts of these materials which cause such artifacts does not seem to have any detectable effect on the other peaks in the Spectra. The problem of the structure of fraction A may now be discussed in greater detail. In the proof of structure for A it was stated that the low intensity of the M-15 peak (1%) compared to that of the M—A3 peak (100%) suggested that an isopropyl group was probably lost 81 from a carbon alpha to the aromatic ring. Whereas, no direct com- parison between the loss of an alkyl group from a carbon alpha to an aromatic ring versus that of the same group being lost from a carbon alpha to oxygen has been presented, there are data on the relative leaving abilities of a methyl versus an isopropyl. In the mass Spectrum for fraction B such a case is presented. In this Spec- trum the M-15 peak has an intensity relative to the base peak of 3.7% whereas the M-A3 peak has an intensity of 79%. The intensity ratio of the M-15 peak to the M—A3 peak is therefore 1 to 21. How- ever, in the mass Spectrum for A this ratio is 1 to 100. In addi- tion to this evidence, the spectra of the model compounds presented and those of similar cases cited from the literature indicated that the loss of an alkyl group from a carbon alpha to an aromatic ring would be favored over the loss of the same group from a carbon alpha to oxygen. Thus, if VII were the correct structure for fraction A, the M-A3 and M-15 peaks would be expected to be much closer in in- tensities than was observed. The facile loss of the C3H7 fragment from the molecular ion of A under the conditions of mass spectrometry therefore allows a clear choice between structures VII and VIII. EXP ERI MENTAL EXPERIMENTAL Elution chromatpgraphy The columns for elution chromatography were packed with either acid-washed aluminum oxide from Merck and Company or l20-500/h mesh polycaprolactam from L. Light Company. Gas Chromatography Gas Chromatography was done on either an Aerograph Model 202 or an aerograph Model A—90-P instrument. The columns were either silicone (SE—30) on Chromasorb W, 20% by weight; ApieamrL on Chrom- asorb W, 10% by weight; or Carbowax on Firebrick, 20% by weight. A11 columns had a 1/A in. external diameter. Thin-layer chromatography Plates for thin-layer chromatography were prepared on 1 X 3 in. microscope slides using Aluminum Oxide G from Research Specialties Company. The plates were developed in an iodine chamber. Infrared spectra The infrared spectra were obtained on either a Perkin-Elmer Model 21 or a Unicam Model SP200 instrument using carbon tetra- chloride solutions in sodium chloride cells. 83 8A Ultraviolet Spectra The ultraviolet spectra were obtained on a Beckman DB Spectro- photometer. Extinction coefficients were calulcated assuming Beer’s law valid. Mass spectra The mass Spectra were obtained on a Consolidated Electrodynamics Model 21-103C Mass Spectrometer. The mass spectra were run by Dr. M. E. Russell, H. H. Harris, and J. F. Wettaw. The intensities of all peaks were assigned values relative to that of the most intense peak of the compound's Spectrum which was assigned the value of 100. NMR spectra The NMR spectra were obtained on a varian Model A—60 instru— ment using tetramethylsilane as an internal standard. The band positions were recorded in T units. The relative peak areas were obtained by electronic integration. Microanalyses A11 microanalytical data were obtained from the Spang Micro- analytical Laboratory, Ann Arbor, Michigan. Melting Points All melting points are uncorrected. 85 Part I The Alkylation Reaction A. Preparation of 2,5-diChloro-2,5—dimethylhexane The procedure of Bruson and Kroeger (6) was followed. A re- action mixture containing 250 g. (1.71 moles) of 2,5-dimethy1-2,5- hexandiol in 700 m1. of concentrated hydrochloric acid was heated and stirred until all the diol had melted. Hydrogen chloride gas was passed through the solution for 20 minutes. The solid which formed upon cooling was collected on a Sintered glass filter. The product was recrystallized from 95% ethanol to give 205 g. (1.11 moles, 65.0%) of white needles melting at 6A-66°. Bruson and Kroeger (6) reported a melting point of 63-6A°. B. Non-catalyzed reaction of 2,5-dichloro-2,5-dimethy1hexane with phenol A mixture of 100 g. (0.55 mole) of 2,5—dichloro—2,5-dimethy1— hexane and 200'g. (2.12 moles) of phenol was heated with stirring at 85-900 for A hours. At the end of that period the evolution of hydrogen chloride had ceased. The mixture was dissolved in ether and extracted with a 200-m1. portion of 10% aqueous potassium hydrox- ide and two 300-m1. portions of Claisen's alkali. The Claisen's alkali was prepared by dissolving 175 g. of potassium hydroxide in 125 m1. of water, cooling, and Slowly adding 500 ml. of methanol. The basic extracts were acidified with hydrochloric acid, then neu- tralized by addition of small portions of solid potassium carbonate. The neutralized extracts were extracted with ether, dried over calcium 86 chloride, filtered, and concentrated by passing a stream of air over the solution. The amounts of reactants and products recovered from the neutral fraction, the 10% aqueous potassium hydroxide extract, and the two Claisen's alkali extracts were 39.90 g., 20.17 g., 6A.61 g., and 51.5A g., reSpectively. Eight product fractions and phenol were detected by thin-layer chromatography and by injecting ether solu- tions of the extracts through a gas chromatograph with a 10 ft. 20% Silicone column at 180° and 215°. These products were designated in the order of their retention times on the column as fractions A—H. The material balance will be discussed in a later part of this thesis. C. Sulfuric acid catalyzed reaction of 2,5-dichloro-2L5-dimethy1— hexane with phenol A melt containing 26.0 g. (0.1A mole) of 2,5-dichloro-2,5- dimethylhexane and 13.3 g. (0.1A mole) of phenol was added dropwise over a l-hour period to 100 m1. of a mechanically stirred solution of 79% sulfuric acid at 10°. The reaction mixture was stirred for 22 hours at room temperature followed by 1 hour at 90°. The mixture was poured into ice—water. This was extracted with ether. The ether Solution was extracted with a 50-ml. portion of 10% aqueous potassium hydroxide and a 50—ml. portion of Claisen's alkali. The basic ex- tracts were acidified with hydrochloric acid and neutralized by addi- tion of small portions of solid potassium carbonate. The neutralized solutions were extracted with ether, dried over calcium chloride, filtered, and concentrated by passing an air stream over the solution. The amounts of the reactants and products obtained from the neutral, 10% aqueous potassium hydroxide, and Claisen's alkali extracts were 87 9.12 g., 6.11 g., and 3.h7 g., respectively. Six product fractions, phenol, and 2,5-dichloro—2,S—dimethylhexane were detected by thin- layer chromatography and by injecting ether solutions of the above extracts into a gas chromatograph with a 10 ft. 20% silicone column at 180° and 215°. The products had identical retention times to those of fractions A and D-H obtained in the non—catalyzed reaction. The material balance will be discussed in a later part of this thesis. Part II. Product Isolation A. Fraction A Fraction A was found largely in the neutral extract of the non- catalyzed reaction where its estimated amount was 6.8 g. (16.8 %). A smaller amount was found in the second Claisen's alkali extract of the non-catalyzed reaction. Trace amounts of A were found in the remaining extracts of the non-catalyzed reaction and the neutral extract of the sulfuric acid catalyzed reaction. A 19.81 9. portion of the neutral extract from the non—catalyzed reaction was eluted on a column containing b95 g. of acid-washed alumina using petroleum ether, benzene, ether, 95% ethanol, and methanol as eluents. Fractions A and E-H were left after concentra— tion of the petroleum ether fractions. Fraction A tended to stay on the column slightly longer than the other four fractions. The seventh and eighth 100-ml. fractions containing 92% and 97% of A, reSpectively, were dissolved in ether and several 50-100 ul. portions of this solution were injected into a gas chromatograph with a 10 ft. 88 20% silicone column at 210° and a helium flow rate of 120 ml. per minute. Pure A was collected at 8.5 minutes after injection. Suf- ficient material was collected to run a neat NMR spectrum. Anal. Calc'd. for Cl4H200: C, 82.30; H, 9.86. Found: C, 82.32; H, 9.87. The infrared, ultraviolet, mass, and NMR spectra of A are shown on pages 12-15. B. Fraction B Fraction B was detected by gas chromatography in all extracts of the non—catalyzed reaction. Its retention time on all columns used was very close to the retention times of fractions C and D which were always found in the extracts containing B. Fraction B comprised approximately 3.7 g. (5.7%) of the first and 0.8 g. (1.5%) of the second Claisen's alkali extract of this reaction. The re- maining two extracts from the non-catalyzed reaction had only trace amounts of B. There was no B detected among the products of the sulfuric acid catalyzed reaction. A 28.75 9. portion of the first Claisen's alkali extract from the non—catalyzed reaction was distilled through a Spinning band ‘column. From this distillation the following fractions were obtained: 12.05 g. of phenol at LS—oSO/L.S mm., 0.5 ml. of fraction 3 at 65—800/0.75 mm., and 15.20 g. of residue. This fraction of B con— tained some phenol. The fraction was poured onto a watch glass which glass which was placed in a vacuum desiccator. The pressure in this desiccator was maintained at 0.1 mm. for 3 hours. The sample 89 of B now contained trace amounts of phenol and fraction A and it contained 15.5% of fraction C. The relative amounts of impurities were determined by injecting an ether solution of this sample of B into a gas chromatograph with a 20 ft. 20% silicone column at 215°. The infrared, ultraviolet, mass, and NMR Spectra of this sample of B are shown on pages 21—2b. C. Fraction C Fraction C was detected by gas chromatOgraphy in all of the extracts from the non-catalyzed reaction. It comprised approximately h.7 g. (7.3%) of the first and 15.8 g. (36.6%) of the second Claisen's alkali extracts and about 26 g. (67.7%) of the neutral extract from this reaction. A trace of C was found in the aqueous potassium hydroxide extract of the non-catalyzed reaction. No C was detected in any of the extracts from the sulfuric acid catalyzed reaction. A 19.81 g. portion of the neutral extract from the non-catalyzed reaction was eluted on a column containing 895 g. of acid-washed alumina using petroleum ether, benzene, ether, 95% ethanol, and methanol as eluents. Fraction C was recovered from the ether and 95% ethanol fractions. A 3.00-g. fraction recovered from ether was found to be more than 99% pure by injecting an ether solution of part of this fraction into a gas chromatograph with a 20 ft. 20% silicone column at 215°. A portion of this fraction was recrystallized from petroleum ether yielding 0.77 g. of white needles melting at l3b—l35°. Anal. Calc'd. for C14H200: C, 82.30; H, 9.86. Found: C, 82.88; H, 9.83. The infrared, ultraviolet, mass, and NMR Spectra of C are shown on pages 27—30. D. Fraction D Fraction D was detected in all of the extracts from both the non-catalyzed and sulfuric acid catalyzed reactions. The Claisen's alkali extract of the sulfuric acid catalyzed reaction was more than 99% pure D. The Claisen's alkali extract from the sulfuric acid catalyzed reaction was recrystallized from ethanol—water yielding white crys- tals of D melting at 182-1830. The infrared, ultraviolet, mass,and NMR spectra of D are shown on pages 32-35. E. Fractions E—H Fractions E-H were found chiefly in the neutral extracts of both the non-catalyzed and sulfuric acid catalyzed reactions. Trace amounts of these compounds were also present in the second Claisen's alkali extract of the non—catalyzed reaction. A 19.81 9. portion of the neutral extract from the non-catalyzed reaction was eluted on a column containing 895 g. of acid-washed alumina using petroleum ether, benzene, ether, 95% ethanol, and methanol as eluents. The fifth 100—ml. fraction recovered from petroleum ether weighed 1.50 g. and was shown by gas chromatography to contain a mixture of E-H only. This fraction was redissolved in a small amount of pentane and 100-ul. portions of this solution were injected into a gas chromatograph with a 20 ft. 20% silicone column at 215° with a helium flow rate of 85 ml. per minute. Small amounts of E melting at 86—880 and H subliming at 215° were collected from 91 these injections. The peaks corresponding to fractions F and G overlapped considerably making it impossible to isolate either of these fractions by this method. A 1.h6 9. portion of the neutral extract from the sulfuric acid catalyzed reaction was eluted on a column containing acid—washed alumina using petroleum ether, cyclohexane, benzene, ether, and 95% ethanol as eluents. The material recovered from the first 50—m1. petroleum ether fraction, weighing 0.18 9., contained fraction G melting at 109—1120. The material recovered from the first 50—m1. cyclohexane fraction, weighing 0.02 g., contained fraction F melting at 101—1050. A check on the purity of these fractions by gas chromatography showed that the sample of F contained about 8% G. The sample of G was greater than 99% pure. Part III. Estimated Yields of Products A through H in the Non— catalyzed and Sulfuric Acid Catalyzed Reactions The yields of products A—H were estimated using several techniques. Products B—D and phenol were separated from the other products and 2,5-dichloro-2,5-dimethylhexane by elution chromatography on acid- washed alumina. The weight of phenol in the first Claisen's alkali extract of the non-catalyzed reaction was obtained by weighing the amount of phenol recovered by distilling this extract through a spin- ning band column. Ether solutions of the extracts and fractions ob— tained by elution chromatography were injected into a gas chromatograph. The relative areas under the peaks on the chromatograms obtained from these injections were determined either by electronic integration 92 or by using a planimeter. Whenever there was incomplete separation of the peaks on these chromatograms the relative areas were estimated by comparing the heights of the peaks. The amount of polymer was estimated from the discrepancy between the amount of phenol recovered from distilling the first Claisen's alkali extract of the non-catalyzed reaction through the spinning band column and the amount of phenol estimated by gas chromatography. Products A-H were assigned a letter corresponding to the order of their retention time on gas chromatography columns. The column and conditions which gave maximum separation was the 20 ft., 1/8 in. diameter, 20% silicone column at 215° and a helium flow rate of 85 ml. per minute. The retention times of the various fractions under these conditions were: solvents and 2,5-dichloro—2,5—dimethy1hexane at 2 minutes, phenol at 3.7 minutes, A at 6.3 minutes, B at 38 minutes, C at 81.3 minutes, D at 88.3 minutes, E at 58.3 minutes, F at 69.3 minutes, 6 at 76.7 minutes, and H at 91 minutes. The peaks for fractions B, C, and D overlapped. The peaks for F and G likewise overlapped slightly. The polymer did not come off as a peak, but temporarily altered the base line of the gas chromatogram. ‘The amounts of the reactants used for both reactions are given in Table 8. The estimated amounts of reactants recovered and products ob- tained for both reactions are listed in Table 5. In the non-catalyzed reaction 88% of the 2,5-dich10ro-2,5-dimethy1hexane was accounted for by these products. Phenol was used in large excess in that reaction. The amounts of products and reactants isolated in the sulfuric acid 93 Table 8. Amounts of reactants Compound Non-catalyzed Sulfuric Acid Catalyzed Phenol 2.12 moles 0.18 mole Bis chloride 0.55 mole 0.18 mole Table 5. Estimated amounts of reactants recovered and products obtained Fraction Non-catalyzed Sulfuric Acid Catalyzed Phenol 830 mmoles (39%) 59 mmoles (82%) Bis chloride none 18 mmoles (10%) A 36 mmoles (6.5%) trace amount 8 23 mmoles (8.2%) none 0 228 mmoles (80.7%) none D 28 mmoles (5.1%) 86 mmoles (33%) E 7.3 mmoles (2.7%) 0.21 mmole (0.30%) F 5.8 mmoles (2.0%) 0.93 mmole (1.38%) 0 8.0 mmoles (2.9%) 2.8 mmoles (8.0%) H 2.5 mmoles (0.9%) 0.19 mmole (0.28%) Polymer 23 %* none ”Based on a monomer unit weight of 208. 98 catalyzed reaction accounted for 89% of the 2,5-dichloro-2,5-di- methylhexane and 78% of the phenol. Phenol was lost during the ex— tractions because of its great solubility in water. The bis chloride was lost because of its high volatility. The bis chloride had a strong sweet odor at room temperature. When heated to a melt a noticeable amount collected on the sides of the container. A con- siderable amount of the unreacted bis chloride was lost by evapora- tion during the concentration of the neutral extract from the sulfuric acid catalyzed reaction. Besides being volatile itself, the bis chloride could decompose into a gaseous alkene and hydrogen chloride when heated. The bis chloride also could hydrolyze to a glycol in the aqueous sulfuric acid solution and this glycol would remain in the aqueous layer during an extraction. Slight alterations in experimental procedure for both reactions, especially the sulfuric acid catalyzed reaction might give a much better material balance. SUMMARY SUMMARY The non-catalyzed aklylation of phenol with 2,5—dichloro—2,5- dimethylhexane yielded eight fractions, designated A-H. The sulfuric acid catalyzed reaction between the same two compounds yielded six fractions which had identical retention times on the gas chromato- graph to those of fractions A and D—H. Samples of each of these fractions were isolated by using one or more separation methods and structures were assigned to the compounds in the several fractions. Fraction A was assigned the structure of 2,2—dimethy1-8-isopropy1- chroman. The two compounds in fraction B were assigned the struc; tures of 1,l—dimethy1-3-i50propy1—5—indanol and 3,3-dimethy1—1-iso- propy1—8—indanol. Fractions C and D were assigned the structures of lph8,8-tetramethy1-5—tetra101 and 1,1,8,8—tetramethyl-6-tetralol, respectively. Fraction E was assigned the structure of 8,8,6,6- tetramethy1—2,8—diiSOpropyl-3,8—dihydroindano[5,6—b]pyran. Fractions F and 0 were assigned the structures of 2,2,6,6,9,9-hexamethy1-8— isoprOpy1-3,8,6,7,8,9-hexahydronaphtho[2,3-bprran and 8,8,6,6,9,9- hexamethyl-2-isopropyl-3,8,6,7,8,9-hexahydronaphtho[2,3-b]pyran, respectively. The two compounds in H were assigned the structures of 1,1,8,8,5,5,8,8—octamethy1—l,2,3,8,5,6,7,8—octa1xydro—9-anthrol and l,1,8,8,5,5,8,8-0ctamethy1-1,2,3,8,5,6,7,8-octahydro—9-phenanthrol. The main compound isolated from the sulfuric acid catalyzed reaction was not l,l-dimethy1-3-isopropyl—S-indanol as postulated by Bruson and Kroeger (6), but was l,1,8,8-tetramethy1—6-tetralol. In fact, 96 97 none of the compounds which they had postulated for the main product was even detected in the reaction mixture. The mechanisms of both reactions were postulated to involve the attack of the tertiary carbonium ion from the bis chloride on either the oxygen or the ortho or para positions of the phenol. A second ionization, followed either by attack on the aromatic ring forming a Six—membered ring, or by rearrangement to a secondary carbonium ion which then attacked the aromatic ring to form a five-membered ring (in the case of an indanol) or a Six-membered ring (in the case of a chroman). This sequence of events was followed in the forma— tion of compounds having the formula C14H200 in fractions A-D. The remainder of the compounds produced had the formula C22H340 and had a mechanism of formation due to two successive cyclialkylations of phenol by the bis chloride. Mass Spectrometry was a useful tool in the elucidation of the several structures. In most cases it totally supported the evidence obtained from the other spectra. In those cases where there were apparent contradictions, the sources of the major peaks on the mass Spectra could be explained from the designated structures in a straightforward manner. LITERATURE CITED 1. 2. 3. 10. 11. 12. 13. 18. 15. 16. 17. 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Chem., 82, 579 (1968). - L. R. C. Barclay, "Cyclialkylation of Aromatics", Friedel-Crafts and Related Reactions, II, 0. A. Olah, Ed., Interscience, New 'York, 1968. W. Reppe and coworkers, Ann., 526, l (1955). H. Hart and J. L. Corbin, J. Am. Chem. Soc., 8:, 3135 (1965). L. R. C. Barclay, A. H. Gray, and C. E. Milligan, Can. J. Chem., ‘39, 870 (1961). 99 19. 20. 21. 100 K. Biemann, Mass Spectrometry, McGraw-Hill, New York, 1962, (a) p. 152. H. Budzikiewicz, C. Djerassi, and D. H. Williams, Interpretation of Mass Spegtra of Organic Compounds, Holden-Day, San Francisco, 19614, m p“ 1630 J. L. Corbin, Ph.D. Thesis, Michigan State University, 1962. F. W. McLafferty, Anal. Chem., 29, 1782 (1957).