3404
X is obtained from eq 1 of Swain and Brown.* A factor of 31.6 is thus estimated as being due simply to the position effect, well within the expected range. It is perhaps worth mentioning that if one plots t;z,y L'S. the log of reactivity for the catalysts of Menger, appending a point corresponding to &,y = 0 and reactivity of 3 1.6 times that of n-butylamine, the correlation coefficient is 0.964 and is, despite only a single degree of freedom, significant at the 0.1 level. Swain and Brown2 made a single measurement using 8-hydroxyquinoline as catalyst and found a kl of only 20 X 10W for a concentration of 0.25 M . The exceedingly low activity of this compound is associated with a coupling index of -0.0126.
In evaluating the results reported here, one must bear in mind the approximate nature of the method used and the fact that certain effects, such as the involvement of the T system of the substrate, are beyond the scope of the Huckel approximation. Further work, both experimental and theoretical, is clearly called for. It seems safe t o conclude, however, that electronic coupling is a factor in bifunctional catalysis. If the reactions of Swain and Brown and of Menger are to be taken as a basis for models of enzyme catalysis, it would seem that such models should include provision for the possibility of coupling through the protein molecule. Further work, using more complete molecular orbital methods, is in progress.
Electrical Effects of Cycloalkyl Groups' Roger C. Hahn, Thomas F. Corbin, and Harold Shechter
Contribution f r o m the Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, and the Department of Chemistry, Syracuse University, Syracuse, New York 13210. Received December 26, 1967 A study has been made of (1) the synthesesand ionization constants of m-and p-cyclopropyl-,-cyclobutyl, -cyclopentyl-,-cyclohexyl-, -(1-cyclopentenyl)-, and -(1-cyclohexenyl)benzoicacids and (2) the syntheses and unimalecular hydrolysis ratesof m-and p-cyclopropyl-,-cyclopentyl-, -cyclohexyl-,andp-cyclobutylphenyldimethylcarbinyl chlorides in 90% aqueous acetone. The effectsof ring size on the ionization constants of the m-(1-cycloalkenyl)and rn-cycloalkylbenzoicacids and on the rates of hydrolysis of m-cycloalkylphenyldimethylcarbinylchlorides are small and are interpreted primarily on the basis of electron release of substituents in the order: cyclohexenyl > cyclopentyl > cyclobutyl > cyclopropyl > 1-cyclohexenyl > 1-cyclopentenyl. p-Cycloalkylphenyldimethylcarbinyl chlorides solvolyze more rapidly than d o their meta isomers; hydrolysis of p-cyclopropylphenyldimethylcarbinyl chloride is much faster than that of its p-cycloalkyl homologs. The marked reactivity of p-cyclopropylphenyldimethylcarbinyl chloride is attributed to stabilization of the reaction transition state through the large 7~ character of the cyclopropyl carbon-carbon bonds. The fact that p-cyclopropylbenzoic acid is weaker than its homologous pcycloalkylbenzoicacids provides additional evidence for the electron-donor abilities of a cyclopropyl group. Abstract:
T
he reactivities of cycloalkyl derivatives are markedly affected by ring size. In order to divorce electrical effects from classical steric factors and to avoid complications arising from carbon skeleton rearrangement of alicyclic substituents, a study has been made of the ionization constants of homologous m- and p-cycloalkylbenzoic acids 1, 2 , 3 , and 4, and the rates of solvolysis of m- and p-cycloalkyl-t-cumyl chlorides 34, 35, 36, and 37.283 The objectives are to determine the electrical effects of cycloalkyl groups in the systems of interest. Synthetic routes to the compounds studied are summarized in Charts I, 11, and 111. The present paper also (1) (a) Abstracted in part from the Ph.D. dissertation of R. C. Hahn, The Ohio State University, Columbus, Ohio, 1960; Dissertafion Abstr., 21, 2891 (1961); University Microfilms, Inc., Ann Arbor, Mich., Library of Congress Card No. Mic 61-911; Chem. Abstr., 55, 18632 (1961). (b) Presented at the 139th National Meeting of the American Chemical Society, St. Louis, Mo., March 21, 1961, Abstracts of Papers, 35-0. (2) L. B. Jones and V. IC=O. Anal. Calcd for ClPHL4: C , 91.08; H, 8.92. Found: C, 90.23; H, 9.71. Nitration of Cyclopropylbenzene (7) (Method 1). Nitric acid (70 ml, 16 N , ca. 1.1 equiv) was added dropwise to a stirred solution of 7 (118 g, 1.0 mol) in acetic anhydride (400 ml) at 10-20". Stirring of the yellow homogeneous mixture was continued for 1 hr at 10". The solution was poured into water and neutralized with cold, concentrated sodium hydroxide. The organic layer and ether extracts of the aqueous layer were combined, washed with excess aqueous potassium carbonate, dried, and concentrated. The yellow residue (156 g, 96%) was combined with 25 g of mononitrated 7 from another run and distilled (ca. 3 mm) through a glasshelix column in three principal fractions: I (o-cyclopropylnitrobenzene, So), bp 99-100", H * ~ D1.5590, 120.7 g; 11, bp 100-115", 20.6 g; 111 (p-cyclopropylnitrobenzene, 8p), bp 115-116", mp 30-31 ', 37.0 g. A mixture of 80 and Sp (bp 81-96" (1-2 mm)) from simple distillation of the nitration product was analyzed. Anal. Calcd for CeHcIN02: C, 66.24; H, 5.56. Found: C, 66.12; H, 5.37. (42) J. Smejkal, J. Jonas, and J. Farkas, Collection Czech. Chem. Commun., 29, 2950 (1964).
Structural assignments were supported by ir spectra; fraction I and o-ethylnitrobenzene showed distinctive absorption near 15.2, 14.3, and 12.8 I*, while fraction 111 and p-ethylnitrobenzene absorbed near 14.5 and 9.0 (sharp). Vapor phase chromatography (5-ft silicone column, 197") and ir spectra each indicated slightly incomplete separation of 80 and 8p in fractions I and 111; purer Sp, mp 32-33" 32-33"), was obtained by recrystallization of 111 from petroleum ether (30-60"). Vpc analysis (100-ft squalene capillary column, 140") of fraction I1 showed only a trace of mcyclopropylnitrobenzene; vpc analysis of the unrectified nitration product gave an 80 to 8p area ratio of 71 :29. Oxidation of a portion of fraction 111with excess 2 0 z nitric acid in phosphoric acid (44 A') gave p-nitrobenzoic acid, mp and mmp 23C-235". Method 2. A solution of 100% nitric acid (0.315 g, 0.005 mol) in acetic anhydride (0.510 g, 0.005 mol) was added dropwise with stirring to a solution of cyclopropylbenzene (1.2 g, 0.01 mol) in acetic anhydride (10 ml) kept at 0-10". After 1-2 hr, water and ether were added to the reaction mixture. The separated ether solution was washed with aqueous sodium hydroxide, dried, and concentrated. Gas chromatography of the resulting mixture (Aerograph Hy-Fi Model 600-C) on a 5-ft silicone rubber column at 180' gave peaks attributable to the isomeric mononitration products. The peak for the meta isomer was obtained by injecting a sample size determined to give maximum on-scale orrko and para peaks at minimum sensitivity and switching to maximum sensitivity for the mefa peak. Retention volumes were assumed equal, and isomer ratios were determined by weighing Xerox cutouts of the vpc scans. Isomer distributions for six runs averaged 26 f 5 % ortho and 74 & 5 para; four of these runs included mefa determinations. which averaged 0.1 i 0.1 %. o-Cyclopropylacetanilide. A mixture of platinum oxide (0.1 g), 80 (50 g, 0.306 mol), and absolute ethanol (40 ml) was shaken under 2-3 atm of hydrogen until practically the theoretical amount had been absorbed. After the catalyst had been filtered and the mixture concentrated at reduced pressure, the residue was distilled to yield o-cyclopropylaniline (90) (38.8 g, 95 %), bp 74-77.5" (2-3 mm), 1 1 2 0 ~ 1.5780. Acetylation (acetic anhydride) gave o-cyclopropylacetanilide, mp 113-114" (recrystallized from ethanolwater), in 92 % yield. Anal. Calcd for CIlHI3NO: C, 75.40; H , 7.48. Found: C, 75.22; H, 7.37. Amine 90 was similarly converted to benz-2-cyclopropylanilide, mp 147-148' (lit.6b 146-147"). 4-Bromo-2-cyclopropylacetanilide (11). A solution of bromine (32 g, 0.20 mol) in glacial acetic acid (150 ml) was poured into 0cyclopropylacetanilide (34 g, 0.194 mol) in acetic acid (200 ml). The initial mildly exothermic reaction soon subsided, and crystals formed; after 4 hr the product was filtered, washed with ether, and dried to give crude 11 (47 g, 95%). Recrystallization (ethanol) yielded a colorless sample, mp 135-1 36 '. Anal. Calcd for CIIH12NOBr: C, 52.00; H, 4.76; Br, 31.46. Found: C, 51.87; H , 4.73; Br, 31.29. p-Cyclopropylacetanilide. Sodium azide (14 g, 0.209 mol) was (33 g, 0.206 mol) added in portions to p-cyclopropylacetophenonelg in 70% sulfuric acid (300 ml) stirred at 15-20'. Nitrogen was evolved rapidly. After 15 min, the mixture was poured into iced water (1 kg). A yellow gum was formed which was taken up in chloroform and dried over potassium carbonate. Most of the solvent was removed at reduced pressure; dilution of the remaining solution with petroleum ether (30-60') produced pale yellow crystals (29 g, Six), mp 115-120'. Recrystallization from benzene afforded a colorless sample of p-cyclopropylacetanilide, mp 120-121 ; admixture with material obtained from acetylation ofp-cyclopropylaniline produced no depression of melting point. Anal. Calcd for Cl1HI3NO: C, 75.40; H, 7.48; N, 7.99. Found: C, 75.61; H, 7.63; N, 8.16. m-Bromocyclopropylbenzene (lorn). Sodium nitrite (19 g, 0.275 mol) in cold water (75 ml) was added slowly to a stirred mixture of 4-bromo-2-cyclopropyIanil~ne hydrochloride (62 g, 0.25 mol, mp 223-225" dec. prepared from 11 in 89% yield43),concentrated hydrochloric acid (75 ml), and water (200 ml) at 5-10". Cold hypophosphorous acid (30%, 560 g, 2.3 mol) was added and the mixture allowed to warm slowly to 25-30". When evolution of nitrogen had ceased, the red organic layer was separated, the aqueous layer was extracted with ethylene dichloride, and the combined organic
z
(43) The procedure used for diazotization was essentially that of C. S. Marvel, H. W. Johnston, J. W. Meier, T. W. Mastin, J. Whitson, and C. M. Himel, J . Am. Chem. Soc., 66, 914 (1944).
Hahn, Corbin,Shechrer
Electrical Effects of Cycioaikyi Groups
341 2 portions were dried over potassium carbonate. After the solution had been filtered and solvent removed, the residue was combined with similar material from other runs and distilled to give colorless bromide 10m (128 g, 94% based on 172 g of amine hydrochloride), ~ dZ541.3888 [lit.4zbp 98-100" (14 bp 63-64" (1-2 mm), n z 5 1.5735, A vapor phase chromatogram (5-ft silicone ~ mm), n Z o 1.57581. column, 219") showed a single peak containing 99% of the total area. Anal. Calcd for C9HnBr: C, 54.86; H, 4.60; Br, 40.55. Found: C,54.69; H,4.92; Br,40.57. m-Cyclopropylbenzoic Acid (lm). A stirred mixture of 10m (9.87 g, 0.050 mol), cuprous cyanide (5.36 g, 0.060 mol), and dimethylformamide (15 ml) was heated at 140" for 1 hr and refluxed for 2 hr. Colorless, slightly impure (contaminated with starting material) m-cyclopropylbenzonitrile (5.97 g, 84%), bp 83-85" (1-2 mm), n 2 0 ~1.5540, was isolated from the red-brown mixture by the procedure described for p-cyclopropylbenzonitrile. After the nitrile had been refluxed 19 hr with 50% ethylene glycol-water (30 ml) containing potassium hydroxide (7.0 g), acid I m was isolated as near-colorless crystals (mp 118-120", 92 % yield) upon acidification. A sequence of recrystallization (ethanol-water), sublimation, and recrystallization yielded colorless needles, mp 121.2-122.0° (lit. 4 2 119-120"), neut equiv calcd 162, found 163, inert to 2 % aqueous potassium permanganate (25-30"). A m / . Calcd for CloH,,O~: C, 74.05; H, 6.22. Found: C, 74.05; H, 6.35. m-Cyclopropylphenyldimethylcarbinol(30m). Treatment of bromide IOm (67 g, 0.34 mol) by the method used for preparation of 30p from lop produced carbinol 30m (41.5 g, 69%), bp 91.5-96" (1-2mm). Acentralfraction[bp95-96"(1-2rnm),n2*D 1.53581was analyzed. Anal. Calcd for C12H160: C, 81.77; H, 9.15. Found: C, 81.44; H , 8.98. 1-Phenylcyclobutanol (12). Cyclobutanone (33.5 g, 0.48 mol) in anhydrous ether (50 ml) was added to a stirred ether solution (300 ml) of phenylmagnesium bromide (0.50 mol) under nitrogen at 0-5". Additional ether (50 ml) facilitated the stirring. After the reaction mixture had been hydrolyzed with aqueous ammonium chloride, the combined ether decantate and residue extract was dried and concentrated at reduced pressure. The partly solid residue was distilled at 75-91" (1-2 mm) and the solid distillate recrystallized (petroleum ether, 30-60") to give large, colorless prisms (44 g, 62%) of alcohol 12, mp 39.0-39.8" (lit. 40-41°,44
_19-40' _
. 45).
Anal. 'Calcd for ClaH120: C, 81.04; H, 8.16. Found:
C, 81.27; H, 8.24. Cyclobutylbenzene (13). Alcohol 12 (15 g, 0.10 mol) in absolute ethanol (50 ml) was hydrogenated over 10% palladized charcoal (ea. 5 g) at 45 psi. After 1 equiv of hydrogen had been absorbed, the mixture was filtered and concentrated and the residue distilled to yield colorless 13 (11.5 g, 89%), bp 88.5-89.5" (30 mm), ~ 2 1.5269, d Z 50.9366 [lit.C6by 101-102" (41 mm), n Z o1.5277, ~ d2Oa 0.9378; bp 89-91" (25 mm), n 2 @ D 1.52671. Vapor phase chromatographic analysis (5-ft silicone column, 155") showed 99 of the area under a single peak. Bromination of Cyclobutylbenzene. Bromide (14.1 g, 0.088 mol) was added in 2 hr to a stirred mixture of 13 (11.5 g, 0.087mol) and iron filings (0.1 g) at 0". After the red mixture had been stirred 2 hr, aqueous sodium hydroxide-sodium sulfite (100 ml) was added. The organic layer and an ether extract of the aqueous layer were combined, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and distilled to give colorless monobromocyclobutylbenzene (15.7 g, 8673, bp 78-80" (1-2 mm), I I D 1.5670, d 2 5 41.3470. Vpc analysis (100-ft squalene capillary column, 150') of the bromocyclobutylbenzene showed two peaks having an approximate area ratio of 13:87 attributable to ortho and pura isomers 140 and 14p,respectively. The infrared spectrum of the mixture contained a strong band at 12.2 p (14p) and a shoulder at 13.25 p (140). Anal. Calcd for CloHllBr: C, 56.89; H, 5.25; Br, 37.86. Found: C, 56.95; H, 5.25; Br, 37.67. p-Cyclobutylbenzoic Acid (2p). Acid 2p was prepared from bromide 14p in 39% over-all yield as depicted in Chart 11, by the methods described for conversion of bromide 10m to acid Im. Properties of the products are given in Table I. (44) J. W. Wilt and D. D. Roberts, J . Org. Chem., 27, 3430 (1962). (45) Yu. S . Shabarov, N. A . Donskaya, and R. Ya. Levina, J . Gen. Chem. USSR,33, 3360 (1963). (46) F. H. Case, J . A m . Chem. Soc., 56, 715 (1934). Journal of the American Chemical S o c i e t y
1
90:13
0
p-Cyclobutylphenyldimethylcarbinol (31p). p,p'-Bicyclobutylphenyl. A mixture of bromides 140 and 14p from bromination of 13 (15.7 g, 0.074 mol) was converted to carbinols 310 and 31p by the process used to prepare 30p from lop. The product mixture (10.0 g, 71%) boiled at 100-102" (1 mm). Analysis by vpc (5-ft silicone column, 165") showed peaks attributable to ortho and para isomers with an area ratio of ca. 14:86. Fractionation through a Nester spinning-band column (1 X 25 cm) produced no detectable separation of isomers; a middle fraction was analyzed. Anal. Calcd for C13H180: C, 82.06; H, 9.53. Found: C, 81.83; H, 9.58. The solid pot residue from the spinning-band fractionation was recrystallized from ethanol as colorless plates, mp 109-111 '; this product was assigned the structure p,p'-bicyclobutylphenyl. Anal. Calcd for C20H22: C, 91.55; H, 8.45. Found: C, 91.75; H, 8.41. 1-(p-Bromopheny1)cyclobutanol (16). Cyclobutanone (1 7.5 g, 0.25 mol) in ether (15 ml) was added in 45 min to a stirred equivalent amount of p-bromophenylmagnesium bromide at 0". The mixture was stirred at 25-30' for 2 hr and then hydrolyzed with saturated aqueous ammonium chloride. The yellow decantate and the ether washings of the residue were combined, dried, concentrated, and distilled to give colorless, impure alcohol 16 (42.6 g, 75 %), bp 90135" (1-2 mm), which subsequently solidified, and an unidentified yellow residue (8 9). Redistillation at 105-108" (1-2 mm) and recrystallization from petroleum ether (30-60") gave colorless crystals of 16, mp 43.544.5". Anal. Calcd for CloHllOBr: C, 52.88; H, 4.88. Found: C, 52.88; H , 4.96. 1-(p-Bromopheny1)cyclobutyl Bromide (17). Alcohol 16 (7.83 g, 0.0345 mol) and hydrobromic acid ( 4 8 z , 50 ml) were shaken at 70-75" for 15 min. The initial crystals soon formed a red-brown oil which crystallized at 25-30". Extraction with petroleum ether (30-60") and recrystallization at 0-5" gave 17 (7.32 g, 7373. Recrystallization from petroleum ether furnished an analytical sample, mp 62-63 3 , which evolved hydrogen bromide on storage for several days. Anal. Calcd for ClOHIOBr2:C, 41.55; H, 3.49; Br, 55.30. Found: C, 41.40; H , 3.54; Br, 55.16. Nitration of Cyclobutylbenzene (13). Nitric acid (4.8 ml, 70%) was added in 15 min to a stirred solution of 13 (6.28 g, 0.0476 mol) in acetic anhydride (33 ml) at 25". After the mixture had been stirred 1 hr at 24", the yellow product (7.07 g, 84%) was isolated as described previously in nitration of 7 : bp 91-102' (1-2 mm), H * ~ D 1.5617. The crude nitration product was rectified (Nester spinningband column); six fractions were collected over the range 102-1 17" (2-3 mm). Refractive indices and infrared spectra indicated that fractions 1 and 6 were nearly pure o-cyclobutylnitrobenzene (150), bp 102-104.8" (2-3 mm), nZoD1.5541, and p-cyclobutylnitrobenzene ( I S p ) , bp 114.5-117" (2-3 mm), n z o 1.5660, ~ respectively. A twice ~ distilled but unrectified sample of similarly nitrated material had ~ da2j1.1306. The mixture corbp 87-88" (1-2 mm), n Z O 1.5587, responded to a 36:64 ortho:para ratio on the basis of its refractive index. Anal. Calcd for CIOHllNO~:C, 67.78; H, 6.26. Found: C, 67.65; H, 6.41. A distilled sample of the mixture of 0- and p-Cyclobutylanilines. 150 and 15p (11.80 g, 0.0667 mol) in absolute ethanol (40 ml) was hydrogenated at 40 psi over 10% palladized charcoal (ca. 4 g) at a maximum temperature of 45'. Three equivalents of hydrogen was absorbed. The mixture was filtered and the filtrate poured into water and extracted with ether. The extract was washed with water and saturated sodium chloride, dried, concentrated, and distilled twice to give a near-colorless liquid, primarily 0- and p-cyclobutylanilines (8.29 g, 84%), bp 78-91' (1-2 mm), n% 1.5700. A middle fraction was analyzed. Anal. Calcd for CIOHIBN:C, 81.58; H, 8.90. Found: C , 81.75; H, 9.17. Hydrogenation of a similar mixture over platinum oxide in ethanol gave 0- and p-cyclobutylanilines in 92% yield, bp 80-91" (1-2 mm). 2(4)-Bromo-4(2)-cyclobutylacetanilides. Potassium acetate (5.9 g, 0.060 mol) in acetic acid (30 ml) and acetic anhydride (22 ml) was added slowly to a stirred mixture of 0- and p-cyclobutylanilines (8.05 g, 0.0547 mol) at 0". The mixture warmed to ca. 25". Bromine (8.8 g, 0.055 mol) in acetic acid (15 ml) was added in 10 min (stirring) at 0-4". The red-orange mixture was stirred for 3.5 Dilution with water precipitated hr while being warmed to 22-25'. an amorphous solid (12.98 g, 89%) which on recrystallization (ethanol-water) afforded a mixture of 2-bromo-4-cyclobutylacetanilide
June 19, 1968
3413 Table 111. Physical Constants and Analyses of Cycloalkyl and Cycloalkenylbenzene Derivatives Compound
p-Cyclobutylbenzonitrile~ p-Cyclobutylbenzoic acid ru-Cyclobutylbenzonitrilea m-Cyclobutylbenzoic acid 1-(p-Bromopheny1)cyclopentene p-( 1-Cyclopenteny1)benzonitrile p-( 1-Cyclopenteny1)benzoic acid p-Cyclopentylbenzoic acid 2-Bromo-4-cyclopentylacetanilided m-Bromocyclopentylbenzene 1-(m-Bromopheny1)cyclopentene m-(I-Cyclopenteny1)benzoic acid m-Cyclopentylbenzoic acid 1-(p-Bromopheny1)cyclohexanol 1-(p-Bromopheny1)cyclohexene p-( 1-Cyclohexeny1)benzonitrilee p-( 1-Cyclohexeny1)benzamide p-( 1-Cyclohexeny1)benzoicacid p-Cyclohexylbenzoic acid m-Bromocyclohexylbenzene 1-(m-Bromopheny1)cyclohexanol 1-(m-Chloropheny1)cyclohexanol 1-(m-Bromopheny1)cyclohexene 1-(m-CIiloropheny1)cyclohexene m-(l-Cyclohexenyl)benzonitrilea m-( 1-Cyclohexeny1)benzoicacid m-Cyclohexylbenzoic acid p-Cyclopentylphenyldimeth ylcarbinol m-Cyclopentylphenyldimethylcarbinol o-Cyclohexylphenyldimethylcarbinol A-Cyclohexyiphenyldimethylcarbinol
Bp, "C (1-2 mm)
Mp, OC
I 1 fD
134.0-134.5 68.5-69.0 96-97 72-73 236-255c 196.5-198.5 143-145 1 .5634e 1 . 6600b
110-1 11 86
124- 26.5i 120- 30 130- 36 102 97 106 110-114 100.5-101.5 130-138 119-121
H
Found, Z C H
Neut equiv Calcd Found
75.0
6.9
74.8
7.0
176
176
75.0 59.2 85.2 76.6 75.8 55.3 58.7 59.2 76.6 75.8 56.5 60.8 85.2 77.6 77.2 76.4
6.9 5.0 6.6 6.4 7.4 5.7 5.8 5.0 6.4 7.4 5.9 5.3 7.2 7.5 7.0 7.9
75.0 59.4 85.1 76.6 76.1 55.8 58.6 59.1 76.4 75.7 56.5 60.9 85.2 77.5 77.5 76.1
7.1 5.2 6.5 6.6 7.3 6.0 5.9 5.0 6.6 7.4 5.8 5.4 7.3 7.3 6.6 7.7
176
175
188 190
189 189
188 190
188 190
202 204
202 205
56.5 68.4 60.8 74.8
5.9 7.2 5.5 6.8
56.4 68.7 61.0 74.6
6.1 7.3 5.5 6.8
77.2 76.4 82.3 82.3 82.5 82.5
7.0 7.9 9.9 9.9 10.2 10.2
77.2 76.3 81.9 81.6 82.4 82.2
6.9 8.0 9.4 9.7 9.7 9.4
202 204
202 205
1 . 5478b
88-92
128-1 31 125-130 123-135
Z
1,5499b
83-85
120-125 100-116
Calcd, C
181.5-182.2f 93.4-94.2 75-76 76-77 67.0-67.8 228-229 203-207 dec 196.5-198.5' 1.55916 51.5-52.0 1.5578* 1.5994b 1 . 5789b11 1.57981 135.5-136.5f 122.4-123.6k 53.5-54.5 1.53246 72.5-73.5 34.5-35.5
~-
~
t = 20". Turned yellow at ca. 225", evolved carbon dioxide at ca. Slightly contaminated with the parent bromide; not analyzed. 250". d Alia/. Calcd for Br: 28.3. Found: 27.4. e t = 25". f Sealed capillaryunder nitrogen. Alia/. Calcdfor N : 7.6. Found: 7.5. h Lit. mp 197": D. Bodroux and R. Thomassin, Bull. Soc. Cliim. France, [5] 6, 1411 (1939). 4-5 mm. 2 Lit. bp 78-89" (0.1 mm), 1 2 2 4 ~1.5782: M. T. Davies, D. F. Dobson, D. F. Hayman, G. B. Jackman, M. G. Lester, V. Petrow, 0. Stephenson, and A. A. Webb, TetraE. W. Garbisch, Jr., J. Org. Cliem., 26, 4165 (1961). & Lit. mp 123-124": J. D hedro/i, 18,751 (1962); bp, 104-107" (1.2 mm), ~ P 1.5783: W. Lynn and L. W. Newton, Cliem. I d . (London), 159 (1958). a
filtered through sodium sulfate, and concentrated. The residue and 4-bromo-2-cyclobutylacetanilide as colorless, cotton-like was diluted with benzene (200 ml), iodine (0.5 g) was added, and 200 crystals in two crops: (1) 10.46 g, 7 1 z , mp 110-180", and (2) ml of distillate was collected. This process was repeated, replacing 0.39 g, mp 110-125". Further recrystallizations did not completely benzene with toluene (200 ml); a total of 7 ml(50% of theory) of separate the isomers. water was azeotroped. Distillation of the residue (bp 120-125", m-Bromocyclobutylbenzene (14m). The mixture of 2(4)-bromo2 mm) and crystallization of the solid distillate from ethanol gave 4(2)-cyclobutylacetanilides (8.76 g, 0.0327 mol) was refluxed 10 hr the olefin as near-colorless plates (110 g, 5 0 z ) . with 95% ethanol (75 ml) and concentrated sulfuric acid (6 ml). Solid sodium nitrite (6.0 g, 0.087 mol) and then water (5 ml, after An attempt to isolate 1-(p-bromopheny1)cyclopentanol (18p)by 0.5 hr) were added at 25-30". On addition of copper powder the subsequent procedure for 18m gave a mixture containing prin(2.5 g, 0.039 mol) in small portions at 35", gases (acetaldehyde, but cipally 1-(p-bromopheny1)cyclopentene. no nitrogen dioxide) were vigorously evolved. After the mixture 1-(m-Bromopheny1)cyclopentene. m-Dibromobenzene (59 g, 0.25 had been refluxed for 15 min, bromide 14m (4.33 g, 6 3 z ) was mol) in ether (50 ml) was added dropwise to a stirred suspension of isolated, bp 67-87 (1-2 mm), as described for the homologous 10m. magnesium (6.1 g, 0.25 mol) in ether (100 ml) under nitrogen at 0 " . Treatment with 2 aqueous potassium permanganate and redistil(Reaction was initiated at 25-30'.) Cyclopentanone (21 g, 0.25 lation afforded colorless 14m,bp 68" (1-2 mm), i P n ~1.5665, P4 mol) was added dropwise to the stirred dark brown solution of m1.3426, infrared bands at 10.9 p (cyclobutane) and 12.8 p (strong, bromophenylmagnesium bromide at 0". After the mixture had broad; nieta substitution), none at 12.2 p (para substitution). been hydrolyzed with aqueous ammonium chloride, the ether Anal. Calcd for CloHllBr: C, 56.80; H, 5.25; Br, 37.86. decantate and the efher washings of the solid residue were filtered Found: C, 56.92; H, 5.27; Br, 37.73. through sodium sulfate and distilled to yield crude light yellow m-Cyclobutglbenzoic Acid ( 2 4 . Acid 2m was prepared from I-(m-bromopheny1)cyclopentanol (18m)(35.5 g, 5 9 z ) , bp 110-120" 14m in 63 over-all yield as depicted in Chart I1 by the procedures (2-3 mm). Subsequent redistillations of successive middle fractions described for the conversion of bromide 10m to acid lm. Products gave a final middle fraction (analyzed), bp 117" (2-3 mm), I Z ~ ~ and properties are given in Table 111. 1.5834, d2s4 1.3922. whose infrared spectrum contained a strong 1-(p-Bromopheny1)cyclopentene. Cyclopentanone (84 g, 10 mol) hydroxyl band. in ether (100 ml) was added to a stirred equivalent of p-bromoAnal. Calcd for CI1H1IOBr: C, 54.89; H, 5.43. Found: C, phenylmagnesium bromide (prepared under nitrogen at - 15 to 55.78; H, 6.14. - 10" from magnesium, p-dibromobenzene, and 40:60 ether-benWeak absorption bands at 5.9 and 6.1 p and analytical data sugzene)?' at 0 " . The viscous addition complex on warming to 25-30" gested that the product contained small amounts of 2-cyclopentylwas hydrolyzed with ice and dilute hydrochloric acid. The ether idenecyclopentanone (from base-catalyzed condensation of cyclolayer and ether extracts of the aqueous layer were combined, expentanone) and 1-(m-bromopheny1)cyclopentene. It was of adtracted with water and with saturated aqueous sodium chloride, vantage to dehydrate the slightly impure product. The method described for dehydration of alcohol 18p was applied to yield an initial product (18.5 g, 84%), bp 80-100" (1-2 mm). Three re(47) This preparation ofp-bromophenylmagnesium bromide is a moddistillations of middle fractions gave colorless 1-(ni-bromophenyl)ification of the method of H. S. Pink, J . Chem. SOC.,123, 3418 (1923).
z
z
Hahn, Corbin, Shechter
1 Electrical Effects of Cycloalkyl Groups
D
3414 cyclopentene which had infrared absorption at 6.1 p (C=C), none for hydroxyl. Physical constants are given in Table 111. 1-(pBromopheny1)cyclohexene and I-(m-Brornopheny1)cyclohexene. Reaction of cyclohexanone and p-bromophenylmagnesium bromide as described for preparation of alcohol 18p (Chart 111) gave 1-(p-bromopheny1)cyclohexanol(19p) in 49 % yield. Dehydration of 19p as described for the cyclopentanol analog yielded l-(pbromopheny1)cyclohexene (97 %). In like manner, 1-(m-bromopheny1)cyclohexene was obtained in 55 % over-all yield from reaction of cyclohexanone with m-bromophenylmagnesium bromide and subsequent dehydration. Physical constants of the products are given in Table 111. p-(1-Cyclopenteny1)benzoic Acid (20p); m-(1-Cyclopenteny1)benzoic Acid (20m); p-(I-Cyc1ohexenyl)benzoic Acid (Zlp); m-(lCyclohexeny1)benzoic Acid (2lm). Acids 20p, 20m, 21p, and 21m were prepared from the corresponding I-(bromopheny1)cycloalkenes as indicated in Chart 111, by the processes used to convert bromide 10m to acid lm (Chart I). Over-all yields ranged from 46% (19p to 2lp) to 72% (18m to 2Om); physical constants and analyses of isolated intermediates are summarized in Table I. Acid 2lp was also synthesized by carbonation of p-(1-cyclohexeny1)phenylmagnesium bromide. Attempted synthesis of acid 21m cia reaction of m-chlorophenylmagnesium bromide with cyclohexanone and subsequent transformations as in Chart 111 gave I-(m-chloropheny1)cyclohexanol (78%) and 1-(m-chloropheny1)cyclohexene (85 %) (Table III), but the latter was converted to the nitrile only in poor yield. p - and m-Cyclopentylbenzoic Acids (3p, 3m). p - and m-Cyclohexylbenzoic Acids (4p, 4m). In a typical procedure, p-(1-cyclopenteny1)benzoic acid (2.3 g, 0.012 mol) in dimethylformamide (5.5 ml) was hydrogenated at ca. 40 psi over 1 0 ~ , p a l l a d i u m on charcoal (ca. 5 g). The mixture absorbed only 1 equiv of hydrogen. After the mixture had been filtered and the catalyst washed. the filtrate was poured into water. Acid 3p separated as a near-colorless amorphous solid (2.3 g, =loo%), mp 191-195'. Crystallization from ethanol-water, treatment with charcoal, and recrystallization gave colorless needles, mp 196.5-198.5 '. Similarly, acids 20m, 21p, and 21m were hydrogenated to give acids 3m, 4p, and 4n1 in yields of 90, 84, and 90%, respectively. Physical constants of the products are given in Table 111. Cyclopentylbenzene (22). Reaction of bromocyclopentane (1 51 g, 1.01 mol) and benzene (360 ml, ca. 4.5 mol) in the presence of anhydrous aluminum chloride (1 g) at 25" and subsequent work-up yielded 22 (115 g, 7773, bp 217-218.5" (lit. 213-215°,4* 215217" 4 g ) , The high-boiling residues (307 g, 1.43 mol based on dicyclopentylb e n ~ e n e ~ Qfrom , ~ o ) several alkylations were combined and refluxed 1 hr with benzene (ca. 6 mol) and anhydrous aluminum chloride (5 g) to give 308 g (73.5%) of 22, identical with material obtained by the previously described method. p-Cyclopentylacetophenone (24). Ketone 24 was prepared from acetyl chloride (173 g, 2.2 mol) and 22 (292 g, 2.0 mol) in ethylene dichloride (1 1.) in the presence of aluminum chloride (280 g, 2.1 mol) at 3-4". The purified product had bp 13C-141" (3-4 mm) [lit,51bp 131-135" (6 mm)]. Vpc analysis (5-ft silicone column, 219 ") indicated a purity of ca. 99 %. p-Cyclopentylphenyldirnethylcarbinol (32p). To a stirred solution of ketone 24 (53 g, 0.28 mol) in dry ether (200 ml) was added 3 A4 methylmagnesium bromide (ca. 100 ml, 0.3 mol) in ether. The mixture was stirred 1 hr and slowly poured into concentrated aqueous ammonium chloride, The organic layer was washed with aqueous ammonium chloride, then with water, dried over anhydrous potassium carbonate, filtered, and concentrated. The residue was distilled at 1-2 mm to give 32p as a pale yellow solid (36 g, 62.6%), bp 110-114", mp 46-49". Recrystallization from petroleum ether (30-60") afforded colorless needles. mp 53.5-54.5 '. A m / . Calcd for C14H200: C, 82.30; H, 9.87. Found: C, 81.90; H, 9.42. p-Cyclohexylphenyldirnethylcarbinol (33p). Reaction of ketone 2S5*lj3and methylmagnesium bromide as described for the cyclo(48) W. Borsche and W. Menz, Ber., 41, 205 (1908). (49) P. V. Hai, Ng. Ph. Buu-Hoi, and Np. D. Xuong, J . Org. Chem., 23, 39 (1958). (50) M. B. Turova-Pollyak and I. R . Davydova, Zh. Obshch. Khim., 26, 2710 (1956). (51) R. D. Ideene, J . Am. Chem. Soc., 71,1893 (1949). (52) R. E. Lutz, R. I
