1944 J . Org. Chem., Vol. 61, No. 6, 1996
Lambert and Ciro
CH2Cl2. To this suspension was added 2 mL of 15% H2SO4.
The solution was stirred for a few minutes, and the above ketal
(2.8 g, 15 mmol) was added dropwise. The reaction was stirred
for 5 h, and the silica gel was filtered and washed with ether.
The solvent was removed by rotary evaporation, and 1.9 g
(89%) of product was obtained: 1H NMR (C6D6) δ 2.0 (s, 8H),
1.4 (s, 6H); 13C NMR (C6D6) δ 210, 126, 124, 40, 27, 20; IR
1715; MS m/z 138 (M+, 100), 123 (20), 109 (10), 96 (50), 81 (100),
67 (51), 53 (23), 41 (33).
between ground and transition states. If the transition
state for elimination is not too early, then hybridization
at the 1 position is moving toward sp2, similar to the kc
transition state that leads to a carbocation. We suspect
that the relatively large isotope effects observed here for
4-OMs, but also for cyclopentyl and for cyclohexyl, are
reflective of hybridization changes in the large elimina-
tion component of the reaction. Because solvent is
present as a base in the transition state for elimination,
such a reaction can give both a relatively high isotope
effect and solvent dependence characteristic of a ks
process in the two-line Raber-Harris plot.
4-Isop r op ylid en ecycloh exa n ol (4-OH). In an oven-dried,
three-necked flask was suspended NaBH4 (0.41 g, 10.8 mmol)
in 20 mL of THF. A solution of the ketone (1.5 g, 10.8 mmol)
in 10 mL of THF was added slowly under N2. The reaction
was refluxed for 4 h and cooled, and 10 mL of H2O was added
slowly. The aqueous layer was extracted three times with
ether. The ether layers were combined and dried (MgSO4),
and the solvent was removed by rotary evaporation. Chro-
matography with silica gel with a 3/1 hexane/ether solvent
Con clu sion s
The introduction of a double bond at the 4 position to
a center of potential production of a carbocation in the
cyclohexane skeleton engenders no through-bond stabi-
lization of positive charge. The mechanism remains ks,
as also found in analogous saturated cyclohexyl systems.
We find no evidence for the σπ/ππ (hyperconjugation/
conjugation) mode of positive charge stabilization, in
contrast to the σπ/σπ (double hyperconjugation) mode in
structurally analogous systems. It is possible that this
result is caused by the less than optimal overlap of the
exo-methylene double bond π orbitals with the ring σ
bonds. Comparison of structure 10 with the ideal de-
picted in Chart 1 suggests deviation from parallelism of
40-50° between the π and σ orbitals. Although this
geometry should not extinguish the effect, it may reduce
it by up to a factor of about four. A more nearly ideal
geometry should be sought to explore the existence of
hyperconjugation/conjugation.
1
mixture produced a white solid: 1.05 g (69%); mp 85 °C; H
NMR (C6D6) δ 3.5 (m, 1H), 2.4 (t, 2H), 1.7 (t, 4H), 1.6 (s, 6H),
1.3 (t, 2H), 1.1 (s, 1H); 13C NMR (C6D6) δ 130, 121, 69, 36, 27,
20; MS m/z 140 (M+, 31), 122 (44), 107 (100), 93 (15), 79 (66),
67 (13), 55 (12), 41 (17). Anal. Calcd for C9H16O: C, 77.05;
H, 11.53. Found: C, 76.46; H, 11.37.
4-Isop r op ylid en ecycloh exa n ol-1-d . The deuterated al-
cohol was made analogously by reducing the corresponding
ketone (1.3 g, 9.4 mmol) with NaBD4 (0.4 g, 9.4 mmol) to give
0.82 g (61%): mp 82 °C; 1H NMR (C6D6) δ 2.5 (m, 2H), 1.7 (m,
2H), 1.59 (s, 6H), 1.3 (t, 2H), 0.75 (s, 1H), 0.45 (s, 1H); 13C
NMR (C6D6) δ 130, 121, 69, 36, 26.9, 20; MS m/z 141 (M+, 30),
123 (47), 108 (100), 94 (14), 80 (62), 67 (16), 55 (12), 41 (20).
tr a n s-4-Isop r op ylcycloh exa n ol (5-OH).18 Commercially
available p-isopropylphenol (6 g, 0.043 mol) was dissolved in
20 mL of 95% EtOH, and rhodium catalyst on an aluminum
support (1 g, 5% Rh) was added. Hydrogenation was carried
out at 60 psi overnight. The reaction was filtered, 10 mL of
H2O was added, and the product was extracted with ether.
The organic layer was washed with 10 mL portions of 5% KOH
and brine and dried over MgSO4. A 50/50 mixture of cis- and
trans-4-isopropylcyclohexanol (5.7 g, 90%) was obtained: MS
m/z 142 (M+, 30), 124 (33), 109 (24), 81 (100), 67 (20), 55 (33),
43 (35).
A small amount of this alcohol mixture was oxidized to the
ketone. Sodium dichromate (0.76 g, 2.5 mmol) was dissolved
in 0.6 mL of concentrated H2SO4 and diluted to 10 mL. This
solution was added slowly to a cooled solution of cis/trans-4-
isopropylcyclohexanol (1 g, 7 mmol) in 20 mL of ether. After
2 h, the product was extracted with ether. Removal of the
solvent yielded 0.4 g (42%) of 4-isopropylcyclohexanone: MS
m/z 140 (M+, 80), 122 (25), 107 (28), 97 (40), 84 (65), 69 (80),
55 (60), 43 (100).
For isomer equilibration, in a three-necked flask under N2,
AlCl3 (3.76 g, 0.028 mol) was suspended in 15 mL of dry ether.
The flask was cooled in an ice bath, and LiAlH4 (0.29, 0.008
mol) in 15 mL of ether was added. To this suspension, the
cis/trans mixture of alcohols (4 g, 0.028 mol) and the previously
made ketone (0.23 g, 1.7 mmol) in 15 mL of ether were added.
The reaction was stirred at gentle reflux overnight and
quenched with H2O, and the product was extracted with ether.
The organic layer was washed with brine and dried (MgSO4),
and the solvent was removed by rotary evaporation. The
product was distilled under vacuum at 45 °C to give 3.0 g (75%)
of a colorless oil. The product was identified by GC as being
91% rich in the trans isomer.
Exp er im en ta l Section
4-(Dibr om om eth ylen e)cycloh exa n on e Eth ylen e Ket-
a l.16 A mixture of commercially available 1,4-cyclohexanedi-
one monoethylene ketal (2.5 g, 0.016 mol), triphenylphosphine
(20.98 g, 0.08 mol), and CBr4 (13.26 g, 0.04 mol) in 200 mL of
dry benzene was stirred at reflux under N2 overnight. The
mixture was cooled to room temperature, the solid material
was removed by filtration, and the filtrate was concentrated
under vacuum. The crude oil was placed in the refrigerator,
and after most of the excess Ph3P had crystallized, the product
was triturated and extracted with hexane. After removal of
the solvent, the crude product was sublimed twice to give 7 g
(70%) of a white solid: 1H NMR (C6D6) δ 1.48 (t, 4H), 2.4 (t,
4H), 3.8 (s, 4H); 13C NMR (C6D6) δ 31.6, 34.5, 64.3, 83.5, 107,
143; MS m/z 310 (M+, 15), 231 (M+ - Br, 100), 152 (10), 99
(17), 83 (6), 55 (5).
4-Isop r op ylid en ecycloh exa n on e Eth ylen e Keta l.16 An
ethereal solution of dimethylcopperlithium was prepared at 0
°C under N2 from cuprous iodide (29 g, 0.15 mol) and 1.4 M
CH3Li (198 mL, 0.27 mol) in 100 mL of ether. To this solution
was added 4-(dibromomethylene)cyclohexanone ethylene ketal
(4.9 g, 0.015 mol), and the reaction was stirred for 4 days at
room temperature. The reaction was cooled to 0 °C, and CH3I
(5 mL) was added very slowly. The reaction was allowed to
warm to room temperature and was stirred for 4 h. The
mixture was poured into 300 mL of saturated aqueous NH4-
Cl. The solid was removed by filtration, and the aqueous layer
was extracted with ether. The combined ether layers were
washed with brine, dried (MgSO4), and filtered, and the solvent
was removed by rotary evaporation. The product was distilled
at 70 °C under vacuum to give 2.8 g (95%) of a clear oil: 1H
NMR (C6D6) δ 3.5 (s, 4H), 2.4 (t, 4H), 1.7 (t, 4H), 1.0 (s, 4H);
13C NMR (C6D6) δ 138, 116, 109, 64, 36, 34, 27; MS m/z 182
(M+, 72), 167 (44), 153 (35), 123 (31), 99 (20), 86 (100), 67 (19),
41 (21).
An ester derivative was prepared for recrystallization by
dissolving 3,5-dinitrobenzoic acid (4.48 g, 0.02 mol) in 80 mL
of dry pyridine. To this solution was added p-toluenesulfonyl
chloride (8.06 g, 0.04 mol). The flask was cooled in an ice bath,
and the trans-rich 4-isopropylcyclohexanol (3.0 g, 0.02 mol)
was added. The reaction was kept cool and was stirred for 2
h. The reaction mixture then was poured into 100 mL of ice-
water. The solid was suction filtered and recrystallized from
hot CH3OH. It was then dried under vacuum to remove traces
of pyridine and recrystallized one more time from hot CH3OH
4-Isop r op ylid en ecycloh exa n on e.17 In a 500 mL, round-
bottomed flask, 34 g of silica gel was suspended in 100 mL of
to give an off-white solid: 4.9 g (70%); mp 120 °C; H NMR
1
(C6D6) δ 0.77 (d, 6H), 0.81 (m, 3H), 1.23 (m, 3H), 1.45 (d, 2H),