[CONTRIBUTION FROM
THE
CHEMISTRYDEPARTMENT OF THE UNIVERSITY OF MISSOURI]
T H E ISOMERIC 4-n-PROPYLCYCLOHEXNOLS' HERBERT E. UNGNADE
AND
ANNA LUDUTSKYa
Received July 14, 19&
4-n-Propylcyclohexanol has been described as a hydrogenation product of a-ethoxypropiovanillone (1), hardwood lignin, and p-propiophenol (2). The products obtained in the three cases were very similar in their physical properties and gave the same phenylurethan or a-naphthylurethan. Since only one derivative was reported, the alcohols evidently consisted mainly of one of the isomers. The present investigation was undertaken in order to determine the configuration of the known alcohol and t o prepare the other isomer. The results of this investigation show that the product of the hydrogenation of p-propiophenol with Raney nickel catalyst consists largely of the trunsalcohol. The pure trans-form was obtained from this mixture by crystallization of the acid phthalate and regeneration of the cyclohexanol. The acid phthalate of the cis-isomer was a glass which proved unsuitable for purification purposes. Attempts to separate the mixture obtained from the hydrogenation of 4-npropylcyclohexanone with platinum in acetic acid failed because the derivatives of the cis-isomer normally used for purification either did not crystallize or else did not form in yields sufficiently large to be practical. The a-naphthylurethans of the two isomeric alcohols could be obtained in good yield from their mixtures and could be separated by fractional crystallization. Regeneration of the pure alcohols by hydrolysis of these compounds appeared unpromising in view of the conditions required for such hydrolysis. It was found, however, that the urethans could be cleaved smoothly without isomerization by ammonolysis with aqueous ammonia under pressure a t 160" (3). The constants of the pure alcohols and of various mixtures are given in the experimental part. EXPERIMENTAL3
The starting material for this investigation was obtained either by reduction ofp-hydroxypropiophenone with Raney nickel catalyst (2) or by reduction of p-n-propylphenol as described in a preceding paper (4). p-n-Propylphenol was prepared from anethole (200 9.) by hydrogenation with Raney nickel (6 g.) at 50' (130 atm.), and demethylation of the crude product (196 g.) with hydriodic acid (d 1.7) (300 cc.), acetic acid (300 cc.), and acetic anhydride (150 cc.). It boiled at 125-126' (20 mm.); yield 171 g. The cyclohexanol prepared by hydrogenation of p-hydroxypropiophenone boiled at 210-212' (740 mm.), and had n! 1.4633, d: 0.9061, MD (calc'd) 43.08, (found) 43.19, T~ 0.549. It gave the following derivatives: a-naphthylurethan, m.p. 134-135', phenylurethan, m.p. 130-130.5" (2), and 3,5-dinitrobenzoate, m.p. 124-125'. 1 Abstracted from a portion of a thesis by Anna Ludutsky, submitted in partial fulfilment of the requirements for the degree of Master of Arts, September 1944. * George Breon Fellow, 1943-1945. * All melting points uncorrected. 520
4-WPROPYLCYCLOHEXANOLS
521
The acid phthalate was prepared according t o Gough, Hunter, and Kenyon (5). It melted a t 115-116' (from petroleum ether). Anal. Calc'd for C1,H2201: C, 70.34, H, 7.58. C, 70.02, H , 7.95. Found : trans-4-n-PropyZcycZohexanoZ.The acid phthalate (11 g., m.p. 115-116') was dissolved in a solution of 6 g. of sodium hydroxide and 60 cc. of water, and the mixture was steamdistilled. The benzene extract of the distillate gave 89.5% of the pure transisomerboiling at 210-212' (747 mm.), and having df 0.8998, n: 1.4605, M D (calc'd) 43.08, (found) 43.26, qtl 0.688. 4-n-Propylcyclohezanone. 4-n-Propylcyclohexanol was oxidized by the method outlined in Organic Syntheses (6). The ketone prepared from 25 g. of the above alcohol mixture weighed 20.4 g. (82%). It boiled at 212' (740 mm.), and had nf 1.4514, d: 0.9049, MD (calc'd) 41.57, (found) 41.69. Anal. Calc'd for CoHlsO: C, 77.09, H, 11.51. Found : C, 76.88, H, 11.67. The semicarbazone, prepared in the usual way, melted at 179.5-180.5" (from aqueous alcohol). Anal. Calc'd for CloHlaNsO: C, 60.85, H, 9.74. Found : C, 60.90, H, 9.79. Reduction of the ketone (20 g.) with sodium (20 g.) and alcohol (250 cc.) gave a product (14.2 g.) boiling at 210-212' (745 mm.), and having n: 1.4609, d: 0.9049, M D (calc'd) 43.08, (found) 43.07, 0.548, a-naphthylurethan, m.p. 134-135'. When the ketone (16 g.) was reduced with platinum in acetic acid containing one drop of hydrochloric acid as described previously (7) the product was partially acetylated as evidenced by its constants: b.p. 221-224", dU 0.9205, n t 1.4475, M, (calc'd for the acetate) 52.33, (found) 53.46. The reaction mixture was therefore refluxed with 50 cc. of 10% alcoholic sodium hydroxide solution in order to hydrolyze the esters. It was extracted with benzene, washed, and distilled. It boiled at 209-210' (742 mm.), and had n: 1.4590, d: 0.9021, MD (calc'd) 43.08, (found) 43.03, $6 0.126, a-naphthylurethan, m.p. 133-134': yield 13.4 g. When t.he alcohol mixture was converted to the acid phthalate, the product consisted of a yellow glass. Its rate of hydrolysis (8) (K = 0.07) was appreciably smaller than that of the pure trans phthalate (m.p. ll5-116", K = 0.23) which is indicative of a high content of cis isomer. The remaining phthalate was therefore fractionally crystallized, a process which proved t o be tedious and time consuming. After removal of numerous small crops of the crystalline trans phthalate (m.p. 115-116") a glass remained (1.49 g.) which could not be crystallized. It yielded 0.5 g. (68.5%) of alcohol which gave a single a-naphthylurethan melting a t 90-91" (from petroleum ether), which depressed the melting point of the isomeric urethan. Anal. Calc'd for CzoHZ6NO2:C, 77.12, H, 8.10. Found : C, 77.09, H, 8.31. cis-4-n-Propylcyclohexanol. Attempts t o obtain the pure cis isomer by hydrogenation of 4-n-propylphenol with platinum in acetic acid under high pressure and at room temperature were unsuccessful. The rate of reduction was greatly increased by raising the pressure which according to Skita (9) should favor formation of the cis isomer, but the product contained appreciable quantities of n-propylcyclohexane (b.p. 50-51') (26 mm.), n," 1.4376, besides the mixture of isomeric alcohols (d: 0.9029, n: 1.4582, $6 0.174) even when the reduction was only 50% complete. There was, however, no evidence of acetylation. The a-naphthylurethan of the cis isomer was prepared in quantity from the alcohol mixture obtained by hydrogenation of the ketone with platinum in acetic acid. The ~
4 The a-naphthylurethan of the trans isomer is formed very readily and due to its great insolubility separates readily from mixtures even if they contain predominantly the cis isomer. The isomeric urethan is easily lost in the mother liquor.
5n
HERBERT E. UNGNADE AND ANNA LUDUTSKY
reaction mixture was heated for two hours a t loo", diluted with petroleum ether and allowed to stand for one week. The urethan of the trans alcohol separated quickly infine needles whereas the isomeric urethan crystallized slowly in clusters. The crystals were separated manually and recrystallized t o constant melting point from petroleum ether. The pure a-naphthylurethan of the cis isomer (m.p. 92-92.S0,5 10 g.) was heated with 100 cc. of concentrated aqueous ammonia for one hour at 160" in an autoclave equipped with a copper liner. The reaction mixture was extracted with benzene and washed free from a-naphthylamine with hydrochloric acid and water. The remaining benzene solution was washed with water, dried, and distilled. The cyclohexanol (3.5 g.) boiled a t 104-105" (20 mm.), and had n: 1.4624, d'," O.QOQS, MD (calc'd) 43.08, (found) 42.85, 1 2 6 0.313. A mixture of 1.6898 g. of this alcohol and 1.6883g. of the trans isomer had the following constants: d: 0.9025, TI: 1.4610, h 4 ~ 43.19, 7%0.456. Inoersion of the cis alcohol. The mixture of alcohols from the hydrogenation of 4-npropylphenol over platinum in acetic acid was rearranged largely to the trans isomer by heating with sodium according t o Vavon (10). The product had the following constants, b.p. 212-214" (740 mm.), n: 1.4610, d:J 0.9016, MD (calc'd) 43.08, (found) 43.23, $6 0.529. On the basis of its physical constants this product was practically identical with the product obtained by reduction of the ketone with sodium and alcohol (11). Some slight inversion took place apparently when the original alcohol mixture was heated to 200" for four hours in a Pyrex flask since both the refractive index and the viscosity increased (n: 1.4582 1.4G01; 726 0.174 -+ 0.191). In view of this instability the pure c 1 isomer ~ vb3s distillet1 only under reduced pressure.
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DISCUSSION OF THE RESULTS
The values of density, refractive index, and molecular refraction of the pure isomeric 4-n-propylcyclohexanols regenerated from crystalline derivatives, are in full agreement with v. ,4uwers' rule (12), according to which the isomer with the higher values for density and refractive index and smaller molecular refraction is cis. With exception of the viscosities, their constants are very similar, so that viscosity measurements mould give the most useful information in regard t o the composition of mistures of the isomers. When the constants of mixtures of the pure isomers were determined they were found, as expected, t o fall beheen the values for the pure isomers. It was, therefore, rather interesting to note that the viscosity of the mixtures rich in the cis isomer (reduction of the ketone with platinum in acetic acid) was much smaller (q16 0.098-0.125, depending on the reduction rates) than that of the pure cis isomer ( $ 5 0.313) or the pure trans isomer ($5 0.688). The refractive index of such mixtcres was lower than that of either isomer whereas molecular refractions of the mixtures agree closely with the calculated value. I t is difficult to account for these results. It may be assumed that the alcohol mixtures obtained by the hydrogenation of the lictone (or phenol) with platinum catalyst contain a third stable isomer of 4-n-propylcyclohexanol which is characterized by low viscosity and a low refractive index. If this assumption is true, the new isomer must be quite unreactive although when forced to react it gives derivatives of the czs isomer. On the basis of these properties the new isomer may represent a stable "boat" fcrm of the cis isomer, and if so, the cis isomer obtained from the a-naphthylurethan must be the corresponding "chair" form. 6
Fisher-Johns block.
4-n-PROPYLCYCLOHEXANOLS
523
SUMMARY
The 4-n-propylcyclohexanolpreviously described in the literature is a mixture of isomers containing predominantly the trans form. The two pure isomers have been prepared by regeneration from purified crystalline derivatives. The mixtures of isomers produced by hydrogenation with platinum catalyst in acetic acid give constants which are different from the pure isomers or their mixtures. In an attempt to explain the results, it is suggested that cis-4-n-propylcyclohexanol may exist in stable boat and chair forms. COLUMBIA, Mo. REFERENCES (1) COOKE, MCCARTHY, AND HIBBERT, J . Am. Chem. Soc., 63, 3052 (1941). D'IANNI,AND ADKINS, J. Am. Chem. SOC.,60,1467 (1938). (2) HARRIS,
(3) BLOCH,BuZZ. aoc. chim., (3)31, 49 (1904). (4) UNGNADE AND NIGHTINGALE, J . Am. Chem. Soc., 66, 1218 (1944). (5) GOUGH, HUNTER, AND KENYON, J . Chem. SOC.,2052 (1926). (6) SANDBORN, Org. Syntheses, Coll. Vol. I, p. 333 (1932). AND LUDUTSKY, J . Org. Chem., 10,307 (1945). (7) UNGNADE Bull. aoc. chim., (4)41, 677 (1927). (8) VAVONAND CALLIER, (9) SKITA,Ber., 64, 2878 (1931). (IO) VAVON,BuZZ. aoc. chim., (5) 4, 1082 (1937). (11) HUCKEL, Ann., 853, 9 (1937). Ann., 420, 91 (1920);SICITA, Ann., 427, 257 (1922);Ber., 85, 1792 (1920). (12) v. AUWERB,
