Solvolysis of 1,1-dimethyl-4-alkenyl chlorides: Evidence for π-participation

Article abstract of DOI:10.1021/jo0107608

Tertiary 1,1-dimethyl-4-alkenyl chloride (1) solvolyzes with significantly reduced secondary β-deuterium kinetic isotope effect (substrate with two trideuteromethyl groups) and has a lower entropy and enthalpy of activation than the referent saturated analogue 4 (k_H/k_D = 1.30 ± 0.03 vs k_H/k_D = 1.79 ± 0.01; ΔΔH^? = -9 kJ mol^-1, ΔΔS^? = -36 J mol^-1 K^-1, in 80% v/v aqueous ethanol), indicating participation of the double bond in the rate-determining step. Transition structure 1-TS computed at the MP2(fc)/6-31G(d) level of theory revealed that the reaction proceeds through a late transition state with considerably pronounced double bond participation and a substantially cleaved C-Cl bond. The doubly unsaturated compound 3 (1,1-dimethyl-4,8-alkadienyl chloride) solvolyzes with further reduction of the isotope effect, and a drastically lower entropy of activation (k_H/k_D = 1.14 ± 0.01; ΔS^? = -152 ± 12 J mol^-1 K^-1, in 80% v/v aqueous ethanol), suggesting that the solvolysis of 3 proceeds by way of extended π-participation, i.e., the assistance of both double bonds in the rate-determining step.

Full text of DOI:10.1021/jo0107608

1490
J . Org. Chem. 2002, 67, 1490-1495
Solvolysis of 1,1-Dim eth yl-4-Alk en yl Ch lor id es: Evid en ce for
π-P a r ticip a tion
Ivica Malnar,† Sandra J uric´,† Valerije Vrcˇek,† Zˇeljka Gjuranovic´,† Zlatko Mihalic´,‡ and
Olga Kronja*,†
Faculty of Pharmacy and Biochemistry, Department of Chemistry, University of Zagreb,
A. Kovacˇic´a 1, P.O. Box 156, 10000 Zagreb, Croatia, and Faculty of Science, Department of Chemistry,
University of Zagreb, Strossmayerov trg 14, 10000 Zagreb, Croatia
kronja@rudjer.irb.hr
Received J uly 26, 2001
Tertiary 1,1-dimethyl-4-alkenyl chloride (1) solvolyzes with significantly reduced secondary
â-deuterium kinetic isotope effect (substrate with two trideuteromethyl groups) and has a lower
entropy and enthalpy of activation than the referent saturated analogue 4 (kH/kD ) 1.30 ( 0.03 vs
kH/kD ) 1.79 ( 0.01; ∆∆Hq ) -9 kJ mol-1, ∆∆Sq ) -36 J mol-1 K-1, in 80% v/v aqueous ethanol),
indicating participation of the double bond in the rate-determining step. Transition structure 1-TS
computed at the MP2(fc)/6-31G(d) level of theory revealed that the reaction proceeds through a
late transition state with considerably pronounced double bond participation and a substantially
cleaved C-Cl bond. The doubly unsaturated compound 3 (1,1-dimethyl-4,8-alkadienyl chloride)
solvolyzes with further reduction of the isotope effect, and a drastically lower entropy of activation
(kH/kD ) 1.14 ( 0.01; ∆Sq ) -152 ( 12 J mol-1 K-1, in 80% v/v aqueous ethanol), suggesting that
the solvolysis of 3 proceeds by way of extended π-participation, i.e., the assistance of both double
bonds in the rate-determining step.
In tr od u ction
the reaction center, in most of the cases no evidence of
π-participation is reported, i.e., kS is considered more
favorable than the k∆ process. For example, Bartlett
demonstrated that in the acetolysis of 5-hexenyl p-
nitrobenzoate, six-membered cyclic products were iso-
lated and the reaction was enhanced in comparison with
its saturated analogue, while in the same reaction with
4-pentenyl p-nitrobenzoate neither rate effect occurred,
nor were cyclized products found.4a However, there are
still a few ambiguous results in which π-participation
cannot be excluded. Thus, Berson showed that in acetoly-
sis of 7-norbornenyl brosylate the formation of the
tricyclic products could be rationalized only if assistance
of the double bond was taken into account.7 Van Tamelen
found 10% of the cyclopentane derivative when 2,3-
epoxynorsqualene was subjected to acid-catalyzed reac-
tion.8 Even though the authors suggest that the process
is very likely SN1-like epoxy-ring opening, followed by
interaction of the resulting carbocation with the neigh-
boring π-electrons, a π-participation mechanism cannot
be ruled out.
A remote double bond which is appropriately placed
toward the reaction center participates in solvolytic
reactions.1 The assistance can result in reduction of the
secondary R- and â-deuterium kinetic isotope effects
(KIEs),2 in enhancement of the solvolytic reactivity,3 in
formation of cyclic products,4 or in lowering the slope of
the Hammett Fσ plot,5 etc. There are many results
published supporting allyl and homoallyl participation
in solvolysis. Solvolysis of substrates with a double bond
at C5 from the reaction center often proceed by way of
anchimeric assistance, forming six-membered rings.4,6
However, if the double bond is placed at C4 relative to
* Tel: +385 1 4818 301. Fax: +385 1 4856 201.
† Faculty of Pharmacy and Biochemistry.
‡ Faculty of Science.
(1) For summary with leading references, see: (a) Lowry, T. H.;
Richardson, K. S. Mechanism and Theory in Organic Chemistry, 3rd
ed.; Harper & Row: New York, 1987; pp 448-486. (b) Isaacs, N. S.
Physical Organic Chemistry, 2nd ed.; Longman: Harlow, 1995; pp
670-677. (c) Borcˇic´, S.; Kronja, O.; Humski, K. Croat. Chem. Acta 1994,
67, 171-188.
(2) For general treatment of isotope effects, see: (a) Collins, C. J .,
Bowman, N. S., Eds. Isotope Effects in Chemical Reactions, ACS
Monograph 167; Van Nostrand Reinhold: New York, 1970. (b) Wolfs-
berg, M. Acc. Chem. Res. 1972, 5, 225-233. (c) Melander, L.; Saunders,
W. H., J r. Reaction Rates of Isotopic Molecules; Wiley: New York, 1980.
(3) (a) Winstein, S.; Shatavsky, M.; Norton, C.; Woodward, R. B. J .
Am. Chem. Soc. 1955, 77, 4183-4184. (b) Winstein, S.; Ordronneau,
C. J . Am. Chem. Soc. 1960, 82, 2084-2085. (c) Bly, R. S.; Bly, R. K.;
Bedenbaugh, A. O.; Vail, O. R. J . Am. Chem. Soc. 1967, 89, 880-893.
(4) (a) Bartlett, P. D.; Closson, W. D.; Cogdell, T. J . J . Am. Chem.
Soc. 1965, 87, 1308-1314. (b) Trahanovsky, W. S.; Doyle, M. P. J . Am.
Chem. Soc. 1967, 89, 4867-4872. (c) Van Tamelen, E. E.; J ames, D.
R. J . Am. Chem. Soc. 1977, 99, 950-952. (d) Bly, R. S.; Bly, R. K.;
Shibata, T. J . Org. Chem. 1983, 48, 101-111.
In our previous communication we showed that, sur-
prisingly, the tertiary chloride 1 had considerably re-
duced secondary â-deuterium KIEs in solvolysis (kH/kD
) 1.30 ( 0.03, in 80% v/v aqueous ethanol, 80E; kH/kD
)
1.29 ( 0.02, in 97% wt/wt aqueous 2,2,2-trifluoroethanol,
97T) compared to its saturated analogue 4 (kH/kD ) 1.79
( 0.01, 80E; kH/kD ) 1.81 ( 0.01, 97T), demonstrating
(6) Sutherland, J . K. In Comprehensive Organic Syntheses; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 3, pp
341-377.
(5) (a) Bartlett, P. A.; Brauman, J . I.; J ohnson, W. S.; Volkmann,
R. A. J . Am. Chem. Soc. 1973, 95, 7502-7504. (b) Mihel, I.; Orlovic´,
M.; Polla, E.; Borcˇic´, S. J . Org. Chem. 1979, 44, 4086-4090. (c) Malnar.
I.; Humski, K.; Kronja, O. J . Org. Chem. 1998, 63, 3041-3044.
(7) Berson, J . A.; Donald, D. S.; Libbey, W. J . J . Am. Chem. Soc.
1969, 91, 5580-5593.
(8) Van Tamelen, E. E.; Pedlar, A. D.; Li, E.; J ames, D. R. J . Am.
Chem. Soc. 1977, 99, 6778-6780.
10.1021/jo0107608 CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/02/2002

Solvolysis of 1,1-Dimethyl-4-Alkenyl Chlorides
J . Org. Chem., Vol. 67, No. 5, 2002 1491
Ta ble 1. Solvolysis Ra te Con sta n ts a n d Activa tion
P a r a m eter s for 1,1-Dim eth yl-1-a lk yl a n d
1,1-Dim eth yl-1-a lk -4-en yl Ch lor id es
t,
k,
∆G*,
∆S*,
c
compd solventa °C 10-4 s-1b ku/ks kJ mol-1d J K-1 mol-1d
4
1
80E
97T
25 0.144e
50 73.5 (6)
45 34.6 (6)
40 25.2 (2)
35 14.10 (5)
30 8.78 (4)
25 5.67 (7)
65 4.84 (2)
60 3.70 (10)
55 2.015 (8)
50 1.334 (19)
45 0.835 (34)
40 0.454 (11)
25 0.0932
55 40.7 (1)
50 34.9 (7)
45 15.62 (3)
40 13.31 (7)
35 6.31 (2)
30 4.89 (9)
25 2.75
-
-
91 ( 4e
78 ( 4
-31 ( 13e
-45 ( 12
the assistance of the double bond in the rate-determining
step.9 Even more surprising was that the KIE observed
for 1 was smaller than the secondary â-deuterium KIE
obtained for chloride 2 (kH/kD ) 1.37 ( 0.03; 80E), in
which the assistance of the double bond has been proven
without ambiguity.10 We proposed the result to be
rationalized in terms of charge distribution in the reac-
tion transition state. Thus, in the case of 1, the transition
state may be more akin to a tertiary cyclopentyl cation
with relatively less charge at the C2, i.e., a “late”
transition state.
To search for a possible participation of the double bond
located at C4 from the reaction center, and for an
extended π-participation with the doubly unsaturated
substrate in which the first double bond is at C4 from
the reaction center, we chose to examine the solvolytic
behavior of protio and hexadeuterated chlorides 1 and
3. Quantum chemical calculations at the MP2(fc)/
6-31G(d) level of theory were also performed to gain an
information about the transition states of the reactions
investigated.
80E
97T
0.6f
82 ( 3
-67 ( 10
-70 ( 21
0.5f
72 ( 7
3
80E
97T
60 4.28 (4)
50 2.13 (9)
40 1.190 (7)
25 0.399
50 19.1 (3)
40 9.45 (7)
30 4.48 (8)
25 3.03
3.7g
-
53 ( 4
56 ( 1
-152 ( 12
-123 ( 1
Resu lts
a
80E is 80% (v/v) aqueous ethanol, and 97T is 97% (w/w)
Su bstr a te P r ep a r a tion . The protio and hexadeuter-
ated isotopomers of chlorides 1, 3, and 4 were prepared
by chlorination (SOCl2) of the parent alcohols. The
unsaturated parent alcohols of 1, and 3, and their
hexadeuterated analogues were obtained by Grignard
addition of CH3I or CD3I to esters 5, and 6, respectively.
b
aqueous 2,2,2-trifluoroethanol. The uncertainty of the last re-
ported figure (standard error) is shown in parentheses. The rate
constants without standard errors are extrapolated values. c Rate
constant of unsaturated vs the corresponding saturated chloride
at 25 °C. Uncertainties are standard deviations. e From ref 17.
d
f The rate of 4 is taken as ks. The rate of the corresponding
g
saturated analogue (k ) 0.108 × 10-4 s-1, ref 17).
Ta ble 2. Secon d a r y â-Deu ter iu m Kin etic Isotop e Effects
of Som e 1,1-Dim eth yla lk yl a n d 1,1-Dim eth yla lk en yl
Ch lor id es a t 50 °C
b
substrate
solventa
80E
t, °C
kH/kD
4c
50
1.79 (1)
1.81 (1)
1.30 (3)
1.29 (2)
1.37 (3)
1.14 (1)
1.17 (2)
1.01 (4)
1
80E
97T
80E
80E
97T
80E
50
30
50
50
30
50
The trans-trisubstituted double bonds in both esters 5
and 6 were introduced according to the well-known
J ohnson procedure.11 The saturated parent alcohol of 4
and its hexadeuterated analogue were prepared by
addition of the Grignard reagent of 1-bromopentane to
acetone and acetone-d6, respectively. All synthetic pro-
cedures are presented in detail in the Experimental
Section.
Kin etic Mea su r em en ts. Chlorides 1, 3, and 4 and
their hexadeuterated analogues 1-d6, 3-d6, and 4-d6 were
subjected to solvolysis in 80% (v/v) aqueous ethanol (80E)
and in 97% (w/w) aqueous 2,2,2-trifluoroethanol (97T).
Solvolysis rates were followed by means of a pH-stat. The
activation parameters were calculated from the rate
constants determined at different temperatures. The rate
2d
3
7e
a
80E is 80% v/v aqueus ethanol; 97T is 97% w/w aqueous 2,2,2-
b
trifluoroethanol. The uncertainties of the last reported figure
(standard deviation of the mean) are shown in parentheses.
c Reference 9. Reference 10. e Reference 18.
d
constants and the activation parameters are presented
in Table 1, while the secondary â-deuterium KIEs are
given in Table 2.
Com p u ta tion a l Meth od s. Geometries were fully
optimized and stationary points were characterized as
minima (no imaginary frequencies) or as transition
structures (one imaginary frequency) by calculation of
the harmonic vibration frequencies. MP2(fc) calculations
were carried out with the GAMESS program,12 employing
(9) Borcˇic´, S.; Kronja, O.; Humski, K.; Miletic´, S. Croat. Chem. Acta
1996, 69, 563-568.
(10) Orlovic´, M.; Borcˇic´, S.; Humski, K.; Kronja, O.; Imper, V.; Polla,
E.; Shiner, V. J ., J r. J . Org. Chem. 1991, 56, 1874-1878.
(11) (a) Ho, N.-h.; Le Noble, W. J . J . Org. Chem. 1989, 54, 2018-
2021. (b) 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. (c)
Kronja, O.; Polla, E.; Borcˇic´, S. J . Chem. Soc., Chem. Commun. 1983,
1044-1045.
(12) Schmidt, M. W.; Baldridge, K. K.; Boatz, J . A.; Elbert, S. T.;
Gordon, M. S.; J ensen, J . H.; Koseki, S.; Matsunaga, N.; Nguyen, K.
A.; Su, S. J .; Windus, T. L.; Dupuis, M.; Montgomery, J . A. J . Comput.
Chem. 1993, 14, 1347-1363.

1492 J . Org. Chem., Vol. 67, No. 5, 2002
Malnar et al.
F igu r e 1. Optimized geometries at MP2(fc)/6-31G(d) of transition structures 1-TS and 2-TS and carbocation intermediates 1-C
and 2-C with some important bond lengths and NBO charges (shown in italics).
6-31G(d) basis set.13 IRC analysis confirmed that the
transition structure located on the energy surface belongs
to the chloride displacement reaction. Atomic charges
were calculated at the MP2(fc)/6-31G(d) level of theory
by a natural population analysis with the NBO program14
built in Gaussian 94.15
The processes of formation of the carbocation interme-
diates from chlorides 1 and 2 were computed considering
that the heterolytic cleavage of the C-Cl bond is ac-
companied by the backside interaction with the neigh-
boring double bond. The energy minimum structures of
chlorides 1 and 2 and the corresponding carbocations 1-C
and 2-C were found as a stationary points. Also, the
transition structures 1-TS and 2-TS were located on the
energy surface. Optimization of 1-TS was difficult be-
cause of the potential energy surface flatness in the
vicinity of the transition structure. In both transition
structures the imaginary frequency is associated with the
dissociation of the C-Cl bond and simultaneous approach
of the double bond. The transition structures 1-TS and
2-TS and the corresponding carbocation intermediates
1-C and 2-C are presented in Figure 1, accompanied with
some important parameters (bond length and NBO
charges).
To test the solvation effects on the computed struc-
tures, single-point self-consistent reaction field (SCRF)
calculations with a polarized continuum model (PCM)
were performed at the MP2/6-31G(d) level of theory.16
A
value of ꢀ ) 30 was used as an input parameter for a
solvent relative permittivity.
P r od u ct An a lysis. The protio derivative of chloride
1 and the protio derivative of referent chloride 2 were
subjected to ethanolysis in 80E in the presence of 2,4,6-
collidine at 25 °C during about 10 halftimes of the
reaction. According to GC analysis, the mixture of the
products isolated consisted of three compounds. The
mixture was separated by column chromatography and
the products were characterized (Scheme 1). Ethanolysis
of the chloride 1 yielded acyclic olefinic alcohol 8 (42%),
and two acyclic unsaturated hydrocarbons 9 (39%) and
(13) The same trends were obtained if 6-311G(d,p) basis set was
used.
(14) (a) Reed, A. E.; Weinstock, R. B.; Weinhold, F. J . Chem. Phys.
1985, 83, 735-746. (b) Reed, A. E.; Curtis, L. A.; Weinhold, F. Chem.
Rev. 1988, 88, 899-926. (c) Glendening, E. D.; Reed, A. E.; Carpenter,
J . E.; Weinhold, F. NBO Version 3.1.
(15) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T. A.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .;
Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian
94, revision E.1, Gaussian, Inc., Pittsburgh, PA, 1995.
(16) Foresman, J . B.; Keith, T. A.; Wiberg, K. B.; Snoonian, J .;
Frisch, M. J . J . Phys. Chem., 1996, 100, 16098-16104.

Solvolysis of 1,1-Dimethyl-4-Alkenyl Chlorides
J . Org. Chem., Vol. 67, No. 5, 2002 1493
Sch em e 1
state, which causes a conversion of some internal rota-
tions to more stiff vibrations. The outcome is the lower
entropy relative to the ground state. Because of the
charge delocalization, less hyperconjugative interaction
between the p orbital of the reaction center and the â-CH-
(D) bonds of the methyl group occurs, resulting in a lower
secondary â-deuterium KIE.
The activation parameters of the unsaturated tertiary
chloride 2 are taken as the referent values for the simple
π-participation mechanism.10 The lower values for 2
compared with 4 (∆∆Hq ) -17 kJ mol-1; ∆∆Sq ) -33 J
mol-1 K-1; 80E)19 are consistent with the mechanism
involving a two π-electron assistance. Also, chloride 2
solvolyzes with a lower secondary â-deuterium KIE than
10 (19%), while chloride 2 produced olefinic alcohol 11
(49%) and two acyclic olefinic products 12 (36%) and 13
(15%), respectively.
the referent chloride 4 (kH/kD ) 1.37 ( 0.03 vs kH/kD
)
1.79 ( 0.01; 80E, Table 2) demonstrating that the partial
positive charge located on the reaction center in the
transition state is smaller.
Discu ssion
Finally, the parameters of the doubly unsaturated
tertiary chloride 7 are the referent values for the ex-
tended π-participation mechanism, in which more exten-
sive charge delocalization (in comparison with 2) results
in further lowering of the enthalpy of activation (∆Hq )
It has been proven in numerous cases that only a large
rate enhancement of the unsaturated compound in
comparison with the saturated analogue (kU/kS . 1) can
be taken as a valid proof of neighboring group participa-
tion.10 Modest or even inverse rate effects can conceal
some considerable assistance, and if this is a case, the
participation or its lack must be proven by other methods.
Solvolytic behavior of the tertiary chlorides 1 and 3 is
such an example where the relative rates obtained are
not decisive parameters (Table 1). Therefore, let us first
establish the referent values of the parameters used here
as reliable criteria in distinguishing the π-participation
mechanism (k∆) (simple or extended) from the double
bond unassisted process (kS), the entropy (∆Sq) and the
enthalpy of activation (∆Hq), and the secondary â-deu-
terium KIE. The later is the most reliable parameter.
Solvolysis of the saturated chloride 4, as other numer-
ous tertiary chlorides, proceeds by way of kS process, in
which nucleophilic solvation occur.17 Thus, the corre-
sponding activation parameters and the â-deuterium KIE
(with 4-d6) represent the referent values for the mecha-
nism unassisted by double bond(s) (Tables 1 and 2). These
values can be used not only to compare the results
obtained for chloride 1 but also for chloride 3, since,
regardless of the chain length, essentially the same
values of activation parameters (∆Hq ≈ 90 kJ mol-1, ∆Sq
≈ -30 J K-1 mol-1; 80E) and exactly the same values of
secondary â-deuterium KIEs (kH/kD ≈ 1.8; hexadeuter-
ated at methyl groups adjacent to the reaction center)
were obtained in solvolysis of numerous dimethylalkyl
chlorides in which the alkyl group varied form ethyl to
squalanyl.10,18 This typical value of the â-deuterium KIE
for the kS process is due to the rate depression for the
deuterated isotopomer caused by hyperconjugative elec-
tron release from the neighboring C-H(D) bond to the
incipient empty p orbital in the transition state.
64 ( 2 kJ mol-1) and the entropy of activation (∆Sq
)
-118 ( 6 J mol-1K-1).20 In addition, extended π-partici-
pation can cause larger volume contraction (-24.0 ( 0.5
cm3 mol-1 for doubly unsaturated vs -13.3 ( 1.0 cm3
mol-1 for the benzylic chloride with one double bond
closely related to 7).11a Nevertheless, the most significant
result is the lack of secondary â-deuterium KIE in
solvolysis of 7 (kH/kD ) 1.01 ( 0.04; 80E, Table 2),
indicating that the hyperconjugative interaction is neg-
ligible, due to the extensive delocalization of the orbital
vacancy from the reaction center.
Sim p le π-P a r ticip a tion . The activation parameters
reported in Table 1 for ethanolysis of chloride show the
same trend in comparison with the corresponding values
for 4 as those for referent chloride 2, demonstrating that
the double bond has an important role in the rate-
determining step in solvolysis. Chloride 1 solvolyzes with
litlle more reduced â-deuterium KIE than the referent
chloride 2 (kH/kD ) 1.30 vs kH/kD ) 1.37; 80E, Table 2). If
that difference between the two effects is real, it could
indicate more effective delocalization of the positive
charge from the reaction center.
The computed transition state structures are in accord
with the conclusion about an important role of the double
bond in the rate-determining step. According to both
transition state model 1-TS and the referent model 2-TS,
the assistance of the double bond results in the formation
of the three-centered bond in which a considerable weak
and elongated C-Cl bonds exists. The principal differ-
ence between structures 1-TS and the referent 2-TS
originates from the degree of the double bond assistance.
In 1-TS the interatomic distances C2-C5 and C2-C6 are
shorter than distances C2-C6 snd C2-C7 in 2-TS, while
the C-Cl bond in 2-TS is shorter than in 1-TS (Figure
1). As was concluded on the basis of the â-deuterium KIE
in a previous communication,9 the computed structures
clearly support that solvolysis of chloride 1 proceeds
through a “later” transition state than the solvolysis of
chloride 2. According to NBO charges, in both transition
In a reaction in which the π-participation mechanism
is operative, a lowering of ∆Hq occurs as a consequence
of charge delocalization in the transition state. Delocal-
ization inevitably involves bridging in the transition
(17) (a) Richard, J . P.; Amyes, T. L.; Vontor, T. J . Am. Chem. Soc.
1991, 113, 5871-5873. (b) Toteva, M. M.; Richard, J . P. J . Am. Chem.
Soc. 1996, 118, 11434-11445. (c) Richard, J . P.; Toteva, M. M.; Amyes,
T. L. Org. Lett. 2001, 3, 2225-2228.
(18) (a) Shiner, V. J ., J r. J . Am. Chem. Soc. 1953, 75, 2925-2929.
(b) Kronja, O.; Orlovic´, M.; Humski, K.; Borcˇic´, S. J . Am. Chem. Soc.
1991, 113, 2306-2308.
(19) Malnar, I. Ph.D. Thesis, University of Zagreb, 1997.
(20) Borcˇic´, S.; Humski, K.; Imper, V.; Kronja, O.; Orlovic´, M.; Polla,
E. J . Chem Soc., Perkin Trans. 1 1989, 1861.

1494 J . Org. Chem., Vol. 67, No. 5, 2002
Malnar et al.
structures 1-TS and 2-TS, a positive charge on the
reaction center C2 is the largest.
The value of the most reliable parameter for 3, the
secondary â-deuterium KIE, is considerably smaller than
that observed for the simple π-participation of 1 but is
larger than the KIE obtained for the referent chloride 7.
Considering that the KIE is here interpreted as a
measure of the charge on the reaction center in the
transition state (methyl groups adjacent to the reaction
center have free rotation), it can be concluded that the
partial charge on the reaction center (C2) in 3-TS is
substantially lower than in 1-TS, but it is also larger than
the charge on the reaction center in the referent 7-TS.
The results obtained in the solvolysis of 3 indicate that
both double bonds take part in the rate-determining step
in the solvolysis of 3. However, the charge in 3-TS is
distributed differently than in 7-TS, i.e., the carbon C2
is more positively charged than in the referent 7-TS.
Efficient charge delocalization could occur from the
optimal preorganized structure, which cannot probably
be achieved in 3-TS because of the angle strain (between
C1, C2, C3, and C4). Similar angle strain is negligible in
7-TS in which the corresponding ring is five-membered.
Therefore, in solvolysis of the model 7, the participation
of the second double bond is more important, the positive
charge is more effectively delocalized, and 7 solvolyzes
with a smaller â-deuterium KIE than 3. The results
obtained could also be interpreted in terms of “early” and
“late” transition states. Unlike with the monounsaturated
models, the “earlier” transition state exists in the case
of 3 and the “later” in the case of 7.
In calculated carbocation intermediates 1-C and 2-C
the positive charge is mainly transferred to the tertiary
carbon atomcs C5 and C6, respectively (Figure 1).
Similarly as in the transition structures, the C2-C5 and
C2-C6 distances are shorter in 1-C than the correspond-
ing C2-C6 and C2-C7 distances in 2-C. Nevertheless,
because of the removal of the positive charge from the
reaction center, cyclized product would be expected,
which is not a case. Despite the theoretical findings, the
lack of the cyclized products is not surprising. That
discrepancy comes from the fact that the solvolyses were
carried out in highly polar solvents (80E and 97T), while
all reported calculations are for the isolated ion in the
gas phase. The solvation effect on all species is not
equally important. While the solvation of the starting
chloride is not significant, the solvation of the positively
charged intermediate is very pronounced. Consequently,
the difference between the computed carbocation struc-
ture in the gas phase and under experimental conditions
is the largest. The results obtained by theoretical calcula-
tion (SCRF)PCM model at the MP2/6-31G(d) level)
clearly support the above assumption about the impor-
tance of the solvation effect in the transition state. In
both cases solvation effects are negligible with chlorides
1 and 2 (∆Gsolv under 1 kcal/mol), while the transition
states 1-TS and 2-TS are stabilized for 27 and 19 kcal/
mol, respectively. Similar trends were recently obtained
by Sorensen et al. in solvation simulation calculations
for the camphenyl and other reference systems.21 It is
well-known that the ion pairs play an important role in
such reactions, so the large fraction of elimination
products might be rationalized if the basicity of the
chloride ion is considered. The chloride can act as a base
and eliminate the hydrogen in its vicinity, yielding the
elimination instead of the cyclized products.
Exp er im en ta l Section
1
Gen er a l. H and 13C NMR spectra were recorded on a 300
MHz spectrometer using CDCl3 as solvent, and IR spectra were
recorded on neat compounds.
Esters 5 and 6 were prepared according to the procedures
described by le Noble et al.,11a which include J ohnson’s
introduction of trans-trisubstituted double bond(s).11b
2,5-Dim eth yl-5(E)-h ep ten -2-ol. The Grignard reagent,
prepared from Mg (1.2 g, 50 mmol) and methyl iodide (7.1 g,
50 mmol) in THF (15 mL), was cooled to 0 °C, and the solution
of ethyl 4-methyl-4(E)-hexenoate (5) (3.88 g, 25 mmol) in 20
mL of THF was added dropwise. The stirring was continued
at room temperature for 1 h. The Grignard complex was
hydrolyzed with saturated aqueous NH4Cl. The water layer
was washed with ether three times, and the combined ether
layers were washed with brine and dried over Na2SO4. The
crude product was distilled under reduced pressure yielding,
Exten d ed π-P a r ticip a tion . The values of activation
parameters and â-deuterium KIE of 3 show that its
solvolytic behavior is different than that of 1 (and 2),
indicating a different reaction mechanism in the solvoly-
sis of 3. Let us examine how the results obtained would
fit if it is presumed that both double bonds take part in
the rate-determining step. Extended π-electron delocal-
ization should cause further lowering of ∆Hq, which is
the case (Table 1). The presumed extended π-participa-
tion mechanism requires a certain conformation in the
transition state, which demands a considerably high
degree of order, and therefore a very negative ∆Sq. Both
values of ∆Sq obtained for 3 (∆Sq ) -152 ( 12 J mol-1
K-1, 80E; ∆Sq ) -123 ( 1 J mol-1 K-1, 97T) and for 7
(∆Sq ) -118 ( 6 J mol-1 K-1; 80E)18 are dramatically
reduced in comparison with the ∆Sq for the corresponding
chlorides 1 and 2, respectively. If the second double bond
takes part in solvolysis of 3, the largest contribution in
decreasing the value of ∆Sq compared with 1 is caused
by the loss of three internal rotations around the three
single C-C bonds located between the two double bonds
in the side chain of 3. The extended π-participation
mechanism fits excellently with the values of ∆Sq, since
it is known that the loss of one internal rotation in the
1
1.36 g (38%) of the pure product. IR 3370 cm-1 (b, O-H); H
NMR (CDCl3) δ 1.22 (s, 6H), 1.54-1.62 (m, 6H), 2.03-2.09 (m,
4H), 5.25-5.27 (m, 1H); 13C NMR (CDCl3) δ 13.76, 15.57, 29.45,
34.3, 41.81, 70.93, 118.28, 135.94.
1,1,1-d 3-2,2,2-d 3-Meth yl-5-m eth yl-5(E)-h ep ten -2-ol. The
procedure is the same as described above. From Mg (0.17 g, 7
mmol), iodomethane-d3 (1 g, 7 mmol), and ethyl 4-methyl-4(E)-
hexenoate (ester 5) (0.55 g, 3.5 mmol), 0.24 g (46%) of product
was obtained. 1H NMR (CDCl3) δ 1.40-1.73 (m, 6H), 2.03-
2.09 (m, 4H), 5.20-5.26 (m, 1H); 13C NMR (CDCl3) δ 13.05,
15.42, 34.18, 34.43, 41.65, 70.54, 118.25, 136.04.
2,5,9-Tr im et h yl-5(E),9(E)-u n d eca d ien -2-ol. The Grig-
nard reagent obtained from Mg (2.0 g, 82.3 mmol) and
iodomethane (6.0 g, 42 mmol) in ether (15 mL) was cooled to
0 °C, and ethyl 4,8-dimethyl-4(E),8(E)-decadienoate (ester 6)
(2.4 g, 10.7 mmol) in ether (20 mL) was added dropwise. The
reaction mixture was heated under reflux (1-2 h). The
Grignard complex was hydrolyzed with saturated aqueous
NH4Cl, and the product was extracted with ether. The
combined ether layers were dried over Na2SO4, the solvent was
evaporated, and the crude product was purified by column
chromatography on silica gel (petroleum ether/dichloromethane
3:1 followed by petroleum ether/dichloromethane 1:1). The
transition state decreases ∆Sq by 15-20 J mol-1 K-1 1c,22
.
(21) Brunelle, P.; Sorensen, T. S.; Teaschler, C. J . Org. Chem. 2001,
66, 7294-7302.
(22) Page, M. I. Chem. Soc. Rev. 1973, 295-323.

Solvolysis of 1,1-Dimethyl-4-Alkenyl Chlorides
J . Org. Chem., Vol. 67, No. 5, 2002 1495
pure alcohol obtained (1.58 g, 79%) was in the form of a viscous
oil. IR (neat) 3370 cm-1 (b, O-H); 1H NMR (CDCl3) δ 1.22 (s,
6H), 1.56-1.62 (m, 9H), 1.99-2.08 (m, 8H), 5.16-5.22 (m, 2H);
13C NMR (CDCl3) δ 13.07, 15.36, 15.76, 28.94, 26.32, 34.30,
39.39, 41.67, 70.99, 118.33, 124.39, 135.32, 135.58.
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 liberated HCl
was continuously titrated by using a 0.008 M solution of NaOH
in the same solvent mixture. Individual measurements 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 3-7
times. Activation parameters were calculated from rate con-
stants at three different temperatures.
1,1,1-d 3-2,2,2-d 3-Meth yl-5,9-d im eth yl-5(E),9(E)-u n d eca -
d ien -2-ol. The procedure is the same as described for the
protio analogue above. From Mg (2.0 g, 82.3 mmol), io-
domethane-d3 (6.0 g 41.4 mmol), and ethyl 4,8-dimethyl-4(E),8-
(E)-decadienoate (2.4 g, 10.7 mmol), 1.57 g (68%) of pure
1
alcohol was obtained. H NMR (CDCl3) δ 1.40-1.73 (m, 6H),
2.03-2.09 (m, 4H), 5.20-5.26 (m, 1H); 13C NMR (CDCl3) δ
13.05, 15.42, 34.18, 34.43, 41.65, 70.54, 118.25, 136.04.
1,1,1-d 3-2,2,2-d 3-Meth yl-2-h ep ta n ol. The procedure is the
same as described for the protio analogue above. From Mg
(0.56 g, 23 mmol), 1-bromopentane (3.47 g, 23 mmol), and
acetone-d6 (1.47 g, 23 mmol), 2.43 g (78%) of pure alcohol was
obtained: 1H NMR (CDCl3) δ 0.96 (t, 3H), 1.16-1.59 (m, 8H);
13C NMR (CDCl3) δ 22.35, 27.62, 27.71, 30.41, 34.67, 43.88,
63.06.
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 0006451).
Ch lor id es 1, 3, a n d 4. 2-Chloro-2,5-dimethyl-5(E)-heptene
(1), 2-chloro-1,1,1-d3-2,2,2-d3-methyl-5-methyl-5(E)-heptene (1-
d6), 2-chloro-2,5,9-trimethyl-5(E),9(E)-undecadiene (3), 2-chloro-
1,1,1-d3-2,2,2-d3-methyl-5,9-dimethyl-5(E),9(E)-undecadiene (3-
d6), 2-chloro-2-methylheptane (4), and 2-chloro-1,1,1-d3-2,2,2-
d3-methylheptane (4-d6) were prepared from the corresponding
alcohols and SOCl2. Alcohol was dissolved in 10-15 mL of
petroleum ether (bp 40-60 °C), and SOCl2 was added dropwise
at -15 °C. The reaction mixture was stirred for 2 h under
reduced pressure (ca. 520-560 mmHg), to remove the liberated
HCl and SO2. The solvent was evaporated and crude chloride
Su p p or tin g In for m a tion Ava ila ble: Coordinates for
transition structures 1-TS and 2-TS and carbocations 1-C and
2-C optimized at the MP2(fc)/6-31G(d) level of theory. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O0107608