Hammett ρ+ Values as Kinetic Evidence for the Concerted Biomimetic Bicyclization Mechanism

Article abstract of DOI:10.1021/jo972237s

Chlorides 1 (1-aryl-1-chloro-5,9-dimethyl-5,9-undecadienes) with various phenyl substituents were prepared (Y = p-OCH₃, p-CH₃, H, p-Br, and m-Br), and solvolysis rates were measured in 80% (v/v) aqueous ethanol and in 97% (wt/wt) aqueous 2,2,2-trifluoroethanol. The Hammett ρ⁺ values obtained are -1.5 and -1.8, respectively, indicating the concerted bicyclization. Comparison with ρ⁺ values that correspond to solvolysis of the benzylic squalene derivatives 3 (ρ⁺ = -1.8 and -1.6 in the same solvents) leads to the conclusion of the concerted bicyclization in 3 and may also suggest concerted bicyclization under biomimetic conditions in the natural precursor, 2,3-epoxysqualene, as well.

Full text of DOI:10.1021/jo972237s

J . Org. Chem. 1998, 63, 3041-3044
3041
Ha m m ett G+ Va lu es a s Kin etic Evid en ce for th e Con cer ted
Biom im etic Bicycliza tion Mech a n ism
Ivica Malnar, Kresˇimir Humski,† and Olga Kronja*
Department of Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb,
Ante Kovacˇic´a 1, 10000 Zagreb, Croatia
Received December 10, 1997
Chlorides 1 (1-aryl-1-chloro-5,9-dimethyl-5,9-undecadienes) with various phenyl substituents were
prepared (Y ) p-OCH3, p-CH3, H, p-Br, and m-Br), and solvolysis rates were measured in 80%
(v/v) aqueous ethanol and in 97% (wt/wt) aqueous 2,2,2-trifluoroethanol. The Hammett F+ values
obtained are -1.5 and -1.8, respectively, indicating the concerted bicyclization. Comparison with
F+ values that correspond to solvolysis of the benzylic squalene derivatives 3 (F+ ) -1.8 and -1.6
in the same solvents) leads to the conclusion of the concerted bicyclization in 3 and may also suggest
concerted bicyclization under biomimetic conditions in the natural precursor, 2,3-epoxysqualene,
as well.
In tr od u ction
tions, not only for model compounds, but also for a
squalene derivative.
The question of the concertedness in biomimetic poli-
cyclization reactions has been discussed for more than
three decades.1-3 Of the two pioneers in this field,
J ohnson4 considered that the concerted mechanism is
possible, while van Tamelen5 stated that only monocy-
clization might be a concerted process and that further
cyclization is stepwise; i.e., the reaction proceeds by way
of mono-, bi-, and tricyclic carbocationic intermediates,
which are separated by energy barriers. van Tamelen
also demonstrated that biomimetic conditions can be used
to rationalize the formation of the first three rings, since
the epoxide ring opening of the 2,3-epoxysqualene, initi-
ated with Lewis acid, produced tricyclic products.6 Re-
cently, several papers appeared generally supporting the
stepwise rings closures.7 Bicyclic and tricyclic carboca-
tion intermediates were trapped in those studies.7b,c
However, monocyclic products were not observed; thus,
the concerted bicyclization cannot be ruled out. In this
paper, we would like to show that concerted biomimetic
bicyclization mechanism is operative in solvolytic condi-
The cases in which concerted bicyclization was estab-
lished with great certainty in solvolysis were the benzylic
chloride 1 with Y ) H, and the tertiary chloride 2, both
systems having the same side chain, with two trans-
trisubstituted double bonds positioned to facilitate the
closure of two six-membered rings, as in the natural
epoxysqualene.8,9 The values of the activation param-
eters obtained in ethanolysis of chloride 1 (∆Hq ) 36 ( 4
kJ mol-1, ∆Sq ) -195 ( 12 J K-1 mol-1
)
)
and the
were all
8
activation volumes (-24.0 ( 0.5 cm3 mol-1
10
consistent only with the extended π-participation mech-
anism. The most significant result that strongly supports
the concerted bicyclization in the case of the tertiary
chloride 2 was the secondary â-deuterium kinetic isotope
effect (KIE), which was drastically reduced.9 Thus, in
the ethanolysis of the saturated analogue of 2 the KIE
was 1.80 ( 0.03. For the corresponding tertiary chloride
with one double bond the effect was considerably reduced
(kH/kD ) 1.37 ( 0.03), suggesting a concerted monocy-
clization. However, under the same conditions, chloride
2 solvolyzed without a significant secondary â-deuterium
KIE (kH/kD ) 1.01 ( 0.04), indicating extended π-partic-
ipation of both double bonds in the rate-determining step.
We considered that evaluating the reaction constant
(Hammett F+)11 for solvolysis of the benzylic system 1
would not only provide an additional test for concerted
bicyclization but, even more important, that value could
be used as a reference in testing for concerted bicycliza-
† Deceased on October 23, 1997.
(1) For a recent review on enzymatic cyclization of squalene and
oxidosqualene, see: Abe, I.; Rohmer, M.; Prestwich, G. D. Chem. Rev.
1993, 93, 2189-2206.
(2) For reviews on polyene cyclizations, see: (a) Taylor, S. K. Org.
Prep. Proced. Int. 1992, 24, 245-284. (b) Sutherland, J . K. In
Compehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: New York, 1991; Vol. 3, pp 341-377. (c) Bartlett, P.
A. In Asymmetric Synthesis; Morrison, J . D., Ed.; Academic Press: New
York, 1984; Vol. 3, pp 341-409.
(3) For a review on kinetic approach to the mechanism of cationic
polyolefinic cyclization, see: Borcˇic´, S.; Kronja, O.; Humski, K. Croat.
Chem. Acta 1994, 67, 171-188 and references therein.
(4) (a) J ohnson, W. S. Tetrahedron 1991, 47(41), xi-xxiii. (b)
J ohnson, W. S. Angew. Chem., Int. Ed. Engl. 1976, 15, 9-17. (c)
J ohnson, W. S. Bioorg. Chem. 1976, 5, 51-98.
(5) (a) van Tamelen, E. E. J . Am. Chem. Soc. 1982, 104, 6480-6481
and references therein. (b) van Tamelen, E. E. Pure Appl. Chem. 1981,
53, 1259-1270.
(6) van Tamelen, E. E.; Willet, J .; Schwartz, M.; Nadeau, R. J . Am.
Chem. Soc. 1966, 88, 5937-5938.
(7) (a) Corey, E. J .; Virgil, S. C.; Cheng, H.; Baker, C. H.; Matsuda,
S. P. T.; Singh, V.; Sarshar, S. J . Am. Chem. Soc. 1995, 117, 11819-
11820. (b) Renoux, J .-M.; Rohmer, M. Eur. J . Biochem. 1986, 155, 125-
132. (c) Boar, R. B.; Couchman, L. A.; J aque, A. J .; Perkins, M. J . J .
Am. Chem. Soc. 1984, 106, 2476-2477.
(8) Kronja, O.; Polla, E.; Borcˇic´, S. J . Chem. Soc., Chem. Commun.
1983, 1044-1045.
(9) Borcˇic´, S.; Humski, K.; Imper, V.; Kronja, O.; Orlovic´, M.; Polla,
E. J . Chem. Soc., Perkin Trans. 1 1989, 1861.
(10) Ho, N.-h.; le Noble, W. J . J . Org. Chem. 1989, 54, 2018-2021.
S0022-3263(97)02237-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/09/1998

3042 J . Org. Chem., Vol. 63, No. 9, 1998
Malnar et al.
Ta ble 1. Solvolysis Ra te Con sta n ts a n d Activa tion
P a r a m eter s for 1-Ar yl-1-ch lor o-5,9-d im eth yl-
5,9-u n d eca d ien es 1 a t 25 °C
Ta ble 2. Lin ea r F r ee En er gy Cor r ela tion of Som e
Ben zylic Ch lor id es a t 25 °C
compd
solvent
na
F+ b
rc
k/
∆Hq/
-∆Sq/
6Sd
6d
97T
97T
5
4
2
5
5
5
5
5
-6.28 (0.25
-3.93 ( 0.10
-6.21
-1.45 ( 0.03
-1.76 ( 0.04
-1.86 ( 0.08
-1.81 ( 0.05
-1.56 ( 0.04
0.997
0.998
compda
solventb
10-4 s-1 c
kJ mol-1 d J K-1 mol-1 d
1-p-OCH3
80E
97T
80E
97T
80E
97T
80E
97T
80E
97T
25.7
119 ( 2
5.10
19.3 ( 0.8
2.06
4.61 ( 0.03 62 ( 2
1.22
2.61
0.46
1.05e
46 ( 4
142 ( 13
1
3
80E
97T
95E
80E
97T
0.999
0.999
0.997
0.999
0.999
1-p-CH3
1-H
46 ( 4
54 ( 4
43 ( 3
151 ( 13
108 ( 13
172 ( 8
100 ( 8
213 ( 8
164.4 ( 0.4
184 ( 17
154f
1-p-Br
1-m-Br
32 ( 3
44.4 ( 0.2
42 ( 4
50f
a
Number of data points with (n ) 5) or without (n ) 4) the
rate of the p-anisyl derivative. For n ) 2 F+ was obtained from
b
p-anisyl and p-toluyl derivatives. Uncertainties are standard
d
errors of estimate. c Coefficient of correlation. Compounds 6 and
a
b
Substituents on the phenyl ring. 80E is 80% (v/v) aqueous
ethanol, and 97T is 97% (wt/wt) aqueous 2,2,2-trifluoroethanol.
c Uncertainties are standard errors. The rate constants without
standard errors are extrapolated values from the data determined
6S, see ref 16.
which the high degree of order that is required in the
transition state (large negative ∆Sq) is overcompensated
by a rather small ∆Hq.13 As we presumed, all substrates
solvolyze by way of extended π-participation, making the
system a reliable model for concerted bicyclization.
π-Participation of neighboring double bond(s) leads to
charge delocalization away from the reaction center.
Thus, the magnitude of the Hammett F+ value, which can
be used as a measure of the charge “seen” by the aromatic
ring at the reaction center,14 the electronic demand,11a
or the charge delocalization,15 should be very indicative
of assistance by neighboring double bonds. The F+ value
for 6 is considerably higher than that for 6S (-3.93 vs
-6.28, Table 2) as expected.16 This is caused by partici-
pation of the neighboring double bond. In the case of the
p-anisyl group, the double-bond assistance is much
attenuated by the strongly electron-donating p-methoxy
substituent. A breakdown of the linear Hammett rela-
tion in the case of the p-anisyl compound (Figure 1)
suggests that the assisted process is the major reaction
pathway for all the variants except the p-anisyl substrate.
That result is not suprising, since the ability of the
p-anisyl group to attenuate double-bond participation has
been previously shown.17
d
at three temperatures. Uncertainties are standard deviations.
e Extrapolated value from the data determined at two tempera-
tures. f Calculated from the data determined at two temperatures.
tion in other systems, where doubt about a mechanism
exists, such as in the solvolysis of 3 and 4. The
importance of the latter structures comes from their
structural relation to the natural precursor of the ste-
roids, squalene.
Resu lts a n d Discu ssion
To obtain the F+ values for the benzylic system 1, a
series of benzylic chlorides 1 were prepared (Y ) p-OCH3,
p-CH3, H, p-Br, and m-Br). The parent carbinols of 1
were obtained using the Barbier addition of bromide 5
(prepared according to the earlier presented proce-
dure10,12) to the corresponding benzaldehydes in the
presence of lithium. The alcohols were converted to
chlorides that were subjected to solvolysis in 80% (v/v)
aqueous ethanol (80E) and in 97% (wt/wt) aqueous 2,2,2-
trifluoroethanol (97T). Reactions were monitored by
titration of the liberated acid with an automatic pH-stat.
Activation parameters were calculated from rate con-
stants determined at three temperatures. The extrapo-
lated or measured rate constants and the activation
parameters are presented in Table 1. The Hammett F+
values for the chlorides 1 were calculated using simple
regression analysis and are presented in Table 2 together
with some other important data.
The F+ values in both solvents for substrates 1 and 3
are much less negative than those of chlorides 6 (Table
2). Also, a better fit is obtained if the p-methoxy variant
of 1 was included in the correlations (Table 2), while
derivatives of structure 6 give a better correlation without
the p-methoxy point. The neighboring group participa-
tion for substrates 1 is not overcome by the p-methoxy
group, supporting a different, extended π-participation
mechanism.
The values of F+ obtained in both solvents (different
nucleophilicity) are essentially the same, excluding the
(11) For reviews, see: (a) Isaacs, N. Physical Organic Chemistry,
2nd ed.; Longman: London, Singapore, 1995; pp 146-192, 451-455,
650-654. See also: (b) Ruasse, M.-F.; Argile, A.; Dubois, J .-E. J . Am.
Chem. Soc. 1984, 106, 4846-4849. (c) Hammett, L. P. Physical Organic
Chemistry; McGraw-Hill: New York, 1970. (d) Brown, H. C.; Okamoto,
Y. J . Am. Chem. Soc. 1958, 80, 4979-4987.
(12) J ohnson, W. S.; Telfer, S. J .; Cheng, S.; Schubert, U. J . Am.
Chem. Soc. 1987, 109, 2517-2518 and refs 10 and 13 cited therein.
(13) To the best of our knowledge there is no other solvolytic reaction
with such a low ∆Hq as that for 1, whose rate can be followed at
conventional temperatures by conventional methods.
(14) Hupe, D. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 451-
464.
(15) (a) J ohnson, C. D. Tetrahedron 1980, 36, 3461-3480. (b) Pross,
The activation parameters obtained in both solvents,
for solvolysis of all chlorides 1, are essentially the same
as for the protio derivative (Y ) H). Thus, all the values
are consistent with rate-determining bicyclization, in
A. Adv. Phys. Org. Chem. 1977, 14, 69-132.
(16) Mihel, I.; Orlovic´, M.; Polla, E.; Borcˇic´, S. J . Org. Chem. 1979,
44, 4086-4090 and ref 2 cited therein.
(17) Gassman, P. G.; Fentiman, A. F., J r. J . Am. Chem. Soc. 1969,
91, 1545-1546 and ref 1 cited therein.

Concerted Biomimetic Bicyclization Mechanism
J . Org. Chem., Vol. 63, No. 9, 1998 3043
the values of F+ for systems 1 and 3 are essentially the
same, leading to the conclusion that the squalene deriva-
tives solvolyze by concerted bicyclization in the rate-
determining step. Drastic reductions in the slope of the
Hammett plots (Figure 1) for each additional double bond
suggest a change in mechanism. Thus, solvolysis of
chlorides 6S proceeds through classical carbocationic
intermediates. With chlorides 6 concerted monocycliza-
tion occurs, while with substrates 1 and 3 concerted
bicyclization takes place. On the other hand, the super-
imposable Hammet plots for 1 and 3 demonstrate that
they use the same reaction mechanism. The inconsistent
values of the activation parameters could be rationalized
using van Tamelen’s22 argument that squalene and some
other polyenes assume a coiled conformation in polar
solvents. Since all the solvents in which the solvolysis
were carried out have high polarity, it is likely that the
squalene-related substrates assume one of the many
coiled conformations in which, by contrast to 1, a neces-
sary degree of order for participation is already achieved
in the ground state. Concerted bicyclization is therefore
favored since there is no requirement for the loss of many
degrees of freedom in the transition state. It is important
to mention that the latest theoretical calculations pre-
sented by J orgensen et al. lead to the same conclusion,
suggesting barrierless concerted formation of A and B
rings from preorganized state of 2,3-epoxysqualene.23
Tricyclization is probably not possible because a very
defined structure in the transition state is needed that
cannot be achieved due to the unfavorable entropy of
activation.
F igu r e 1. Hammett plots for some benzylic chlorides in 97%
(wt/wt) aqueous 2,2,2-trifluoroethanol at 25 °C.
possibility that this extremely significant result is due
to rate determining displacement by the solvent.18 All
the results can be attributed to the relatively small
partially positive charge on the benzylic carbon of the
transition state, since the charge is delocalized on at least
five carbon atoms in concerted bicyclization, as is shown
in structure 7. Larger charge delocalization from the
benzylic carbon in the transition state of 1 is consistent
with the drastically less negative value of F+ with an
additional double bond (from -3.9 to -1.8 in 97T).
Exp er im en ta l Section
Gen er a l Meth od s. All reactions requiring anhydrous
conditions were carried out under inert atmosphere (argon).
Dichloromethane (CH2Cl2) was dried over molecular sieves 4A.
Tetrahydrofuran (THF) and diethyl ether (ether) were distilled
and dried over sodium. The petroleum ether used had a
boiling range of 40-60 °C. Whenever required, the reactions
were conducted in oven-dried glassware under dry argon. For
column chromatography, Merck silica gel (mesh 70-230) was
used. TLC was performed on silica gel-coated plastic sheets
(Merck TLC-plastic sheets silica gel 60) with vapors of I2 as
detector. 1H and 13C NMR spectra were recorded on a 300
MHz spectrometer using CDCl3 as solvent. Chemical shifts
are reported in ppm (δ) relative to Me4Si as an internal
standard. IR spectra (cm-1) were measured on neat com-
pounds.
Con cer ted Bicycliza tion of Squ a len e Der iva tives.
Unlike the results for the model structures 1 and 2, which
are all consistent with a concerted bicyclization, mea-
surements with the squalene derivative are ambiguous
in some aspects. For both systems 3 and 4 the activation
parameters are in the range assigned to concerted
monocyclization.19-21 However, other parameters strongly
support the extended π-participation mechanism. Etha-
nolysis of chloride 4 and its protio analogue gave a
secondary â-deuterium KIE near unity (kH/kD ) 1.02 (
0.01).21 The identical result was obtained for 2, leading
to the conclusion that the squalene derivative also
undergoes concerted bicyclization. The Hammett F+
values obtained in three solvents with chlorides of the
benzylic squalene derivatives 3 were much less negative
than F+ for the chlorides 6 (Table 2).20 These values
clearly suggest the extended π-participation mechanism,
but it was not possible to decide whether bicyclization
or even tricyclization is operative. It is evident from the
data presented in Table 2 and shown in Figure 1 that
1-Br om o-4,8-d im et h yl-4,8-d eca d ien e. Procedures de-
scribed by le Noble et al.,10 which include J ohnson’s12 introduc-
tion of two trans trisubstituted double bonds, were used. A
reaction scheme with almost the same procedure was pub-
lished earlier by our group.8 A novel procedure for preparation
and purification of bromide 5 was employed that was described
1
in our previous paper,20 with 95.1% yield. H NMR (CDCl3) δ
1.56-1.59 (m, 9H, CdCCH3), 1.91-2.13 (m, 8H, CCH2C), 3.35
(t, 2H, J ) 6.74 Hz, CH2Br), 5.13-5.21 (m, 2H, CdCH); 13C
NMR (CDCl3) δ 13.10, 15.33, 15.53, 26.28, 30.63, 33.06, 37.60,
39.38, 118.44, 125.74, 132.80, 135.40.
1-P h en yl-5,9-d im eth yl-5,9-u n d eca d ien ol. A suspension
of lithium (Li) powder (300 mg, 43.22 mmol), granulated Li
(300 mg, 43.22 mmol), dry THF (5 mL) and very little (10 µL)
CH3I was refluxed under a slow stream of argon for 10-15
min. The flask was placed in the ultrasonic bath (100 W, 30
kHz), and then a solution of bromide 5 (1.2 g, 4.89 mmol) and
(18) (a) Harris, J . M.; Schadt, F. L.; Schleyer, P. von R.; Lancelot,
C. J . J . Am. Chem. Soc. 1969, 91, 7508-7510 and ref 1a cited therein.
(19) Malnar, I.; Kronja, O.; Humski, K.; Borcˇic´, S. Croat. Chem. Acta
1992, 65, 547-549.
(20) Borcˇic´, S.; Humski, K.; Kronja, O.; Malnar, I. Croat. Chem. Acta
1996, 69, 1347-1359.
(21) Kronja, O.; Orlovic´, M.; Humski, K.; Borcˇic´, S. J . Am. Chem.
Soc. 1991, 113, 2306-2308 and ref 13 cited therein.
(22) van Tamelen, E. E. Acc. Chem. Res. 1968, 1, 111-120 and ref
8 cited therein.
(23) J enson, C.; J orgensen, W. L. J . Am. Chem. Soc. 1997, 119,
10846-10854.

3044 J . Org. Chem., Vol. 63, No. 9, 1998
Malnar et al.
benzaldehyde (0.432 g, 4.07 mmol) in 50 mL of dry THF was
added dropwise to the stirred mixture. The temperature was
held around 0 °C. After all the solution was added, the
reaction mixture was by turns stirred with the magnetic stirrer
and the ultrasonic bath for additional hour. The progress of
the reaction was checked by TLC. During that period of time
the color of the Li surface changed from dull matt to a golden
silvery sheen. The excess of Li was filtered off, the filtrate
was treated with a saturated aqueous solution of NH4Cl (three
times), and the alcohol was extracted three times with ether.
The ether layers were combined, washed with a saturated
aqueous solution of NaHCO3 (three times), and dried over
anhyd Na2SO4. The ether was evaporated, and the product
was purified on a silica column. Unreacted bromide was
removed with petroleum ether, other impurities were removed
with petroleum ether/CH2Cl2 mixture (4:1), and the pure
alcohol was eluted with petroleum ether/CH2Cl2 mixture (1:
1). Evaporation of the pooled alcohol-containing fractions
yielded 205.85 mg (18.56%) of the pure product: IR (neat) 3410
cm-1 (b, OH); 1H NMR (CDCl3) δ 1.56-1.60 (m, 9H, CdCCH3),
1.97-2.06 (m, 10H, CCH2C), 4.66 (t, 1H, J ) 6.46, Ph(OH)-
CH), 5.10 (t, 1H, J ) 6.45, dCHCH2-), 5.20 (q, 1H, J ) 6.46,
dCHCH3), 7.30-7.35 (m, 5H, Ph); 13C NMR (CDCl3) δ 13.05,
15.36, 15.47, 23.71, 26.29, 38.24, 39.13, 39.46, 74.39, 118.21,
124.54, 125.80, 127.37, 128.32, 134.55, 135.63, 144.85.
1-(4-Met h oxyp h en yl)-5,9-d im et h yl-5,9-u n d eca d ien ol.
The procedure is the same as described above. From 200 mg
(29 mmol) of powdered Li, 200 mg (29 mmol) of granulated
Li, 1.2 g (4.9 mmol) of bromide 5, and 0.56 g (4.1 mmol) of
anisaldehyde was obtained 220.9 mg (17.8%) of pure alcohol:
IR (neat) 3430 cm-1 (b, OH), 3430 (O-H); 1H NMR (CDCl3) δ
1.54-1.59 (m, 9H, CdCCH3), 1.94-2.04 (m, 10H, CCH2C), 3.78
(s, 3H, p-CH3O), 4.57 (t, 1H, J ) 6.6, Ar(OH)CH), 5.08 (t, 1H,
J ) 6.45, dCHCH2-), 5.18 (q, 1H, J ) 6.46, dCHCH3), 6.85
(d, 2H, J ) 8.7, m-CHAr), 7.23 (d, 2H, J ) 8.7, o-CHAr); 13C
NMR (CDCl3) δ 13.02, 15.33, 15.44, 23.75, 26.26, 38.12, 39.12,
39.42, 54.96, 73.90, 113.58, 127.03, 134.57, 136.98, 118.16,
124.43, 135.60, 158.83.
2H, J ) 8.14, m-CHAr); 13C NMR (CDCl3) δ 13.05, 15.36, 15.47,
23.52, 26.28, 38.26, 39.06, 39.44, 73.70, 118.22, 124.68, 125.80,
128.34, 134.38, 127.54, 131.40, 143.81.
1-(3-Br om oph en yl)-5,9-dim eth yl-5,9-u n decadien ol. The
procedure is the same as described above. From 150 mg (21.6
mmol) of powdered Li, 400 mg (57.6 mmol) of granulated Li,
1.89 g (7.7 mmol) of bromide 5, and 1.18 g (6.4 mmol) of
3-bromobenzaldehyde was obtained 90.15 mg (4.0%) of pure
alcohol: IR (neat) 3400 cm-1 (b, OH); 1H NMR (CDCl3) δ 1.55-
1.60 (m, 9H, CdCCH3), 1.99-2.06 (m, 10H, CCH2C), 4.66 (t,
1H, Ar(OH)CH), 5.12-5.21 (m, 2H, dCHCH2- and dCHCH3),
7.34-7.51 (m, 4H, CHAr); 13C NMR (CDCl3) δ 13.07, 15.34,
15.54, 25.94, 26.25, 30.40, 35.73, 39.39, 39.44, 65.08, 118.34,
124.76, 125.22, 126.91, 127.54, 128.48, 130.46, 134.54, 135.58,
140.86.
Ch lor id es 1. 1-Chloro-1-phenyl-5,9-dimethyl-5,9-undeca-
diene (1-H), (1-chloro-1-(4-methoxyphenyl)-5,9-dimethyl-5,9-
undecadiene (1-p-OCH3), 1-chloro-1-(4-methylphenyl)-5,9-
dimethyl-5,9-undecadiene (1-p-CH3), 1-chloro-1-(4-bromophenyl)-
5,9-dimethyl-5,9-undecadiene (1-p-Br), and 1-chloro-1-(3-
bromophenyl)-5,9-di-methyl-5,9-undecadiene (1-m-Br), respect-
ively, were prepared from the corresponding alcohols and
thionyl chloride (SOCl2). The appropriate alcohol was dis-
solved in 10-15 mL of petroleum ether (bp 40-60 °C), the
solution was cooled to -15 °C, and SOCl2 was added dropwise.
The reaction mixture was stirred for 2 h under reduced
pressure (about 520-560 mmHg, 693-747 mbar) to remove
the liberated HCl and SO2 continuously. Then, the petroleum
ether was evaporated and crude chloride was used for kinetic
measurements. Further purification proved to be unnecessary
since the solvolysis rates were found to be independent of
contamination.
Kin etic Mea su r em en ts. Solvolysis rates were followed in
80% (v/v) aqueous ethanol (80E) and 97% (wt/wt) aqueous
2,2,2-trifluoroethanol (97T) titrimetrically by means of a pH-
stat (end-point titration, pH ) 6.85). Typically, 0.02 mmol of
the chloride 1 was dissolved in 20 mL of the solvent at the
required temperature thermostated (0.05 °C, and the liber-
ated HCl was continuously titrated by using a 0.008 M solution
of NaOH in the same solvent mixture. Individual measure-
ments could be described by the first-order low from 15% up
to at least 80% completion. First-order rate constants were
calculated from about 100 determinations by using a nonlinear
least-squares program. Measurements were usually repeated
three to seven times. Activation parameters were calculated
from rate constants at three different temperatures.
1-(4-Meth ylph en yl)-5,9-dim eth yl-5,9-u n decadien ol. The
procedure is the same as described above. From 270 mg (38.9
mmol) of powdered Li, 220 mg (31.7 mmol) of granulated Li,
1 g (4.08 mmol) of bromide 5, and 0.41 g (3.41 mmol) of
p-toluylaldehyde was obtained 258 mg (26,5%) of pure alco-
1
hol: IR (neat) 3390 cm-1 (b, O-H); H NMR (CDCl3) δ 1.54-
1.58 (m, 9H, CdCCH3), 1.94-2.07 (m, 10H, CCH2C), 2.32 (s,
3H, p-CH3-), 4.57 (t, 1H, J ) 6.6, Ar(OH)CH), 5.08 (t, 1H,
dCHCH2-), 5.18 (q, 1H, dCHCH3), 7.12 (d, 2H, J ) 7.86,
m-CHAr), 7.19 (d, 2H, J ) 7.86, o-CHAr); 13C NMR (CDCl3) δ
13.02, 15.34, 15.47, 23.75, 26.29, 38.18, 39.15, 39.46, 20.80,
74.18, 118.17, 124.46, 134.58, 135.61, 136.94, 125.76, 128.97,
141.90.
Ack n ow led gm en t. We gratefully acknowledge the
financial support of this research by the Ministry of
Science and Technology of the Republic of Croatia
(Grant No. 006151).
1-(4-Br om oph en yl)-5,9-dim eth yl-5,9-u n decadien ol. The
procedure is the same as described above. From 270 mg (38.9
mmol) of powdered Li, 260 mg (37.5 mmol) of granulated Li,
1.2 g (4.9 mmol) of bromide 5, and 0.75 g (4.08 mmol) of
4-bromobenzaldehyde was obtained 130.4 mg (9.12%) of pure
alcohol: IR (neat) 3490 cm-1 (b, OH); 1H NMR (CDCl3) δ 1.55-
1.59 (m, 9H, CdCCH3), 1.96-2.05 (m, 10H, CCH2C), 4.63 (t,
1H, J ) 6.46, Ar(OH)CH), 5.09 (t, 1H, J ) 6.46, dCHCH2-),
5.19 (q, 1H, dCHCH3), 7.21 (d, 2H, J ) 8.14, o-CHAr), 7.46 (d,
Su p p or tin g In for m a tion Ava ila ble: Spectral data and
C, H, N analysis for bromide 5 and all parent alcohols of 1 (19
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O972237S