ortho-Effect on the acid-catalyzed hydration of 2-substituted α-methylstyrenes

Article abstract of DOI:10.1135/cccc2008115

α-Methylstyrene and nine ortho-substituted analogs have been synthesized and the kinetics of their acid-catalyzed hydration in aqueous solutions of sulfuric acid at 25°C have been investigated. The kinetic acidity function H_S has been constructed from the dependence of the observed rate constants k_obs on the sulfuric acid concentration. The catalytic rate constants of the acid-catalyzed hydration k_ortho have been calculated as well. The identical shape of the kinetic acidity functions for ortho- and para-derivatives confirms what the consistent mechanism A-SE2 of the acid-catalyzed hydration has already proved for the corresponding paraderivatives. The A-SE2 mechanism involves a rate-determining proton transfer of the hydrated proton to the substrate. From the dependence of the catalytic rate constants of the ortho-derivatives on the catalytic rate constants of the para-derivatives, it is seen that the logarithm of the catalytic rate constant for hydrogen as a substituent is markedly out of the range of the other substituents and, simultaneously, that the ortho-derivatives react significantly slower than the corresponding para-derivatives. In correlation with the substitent constants σ_p⁺, a reaction constant of ρ⁺= -1.45 have been found. The constant is, in absolute value, considerably smaller than that for para-derivatives (ρ⁺ = -3.07). In parallel, the steric effects are enforced more significantly for the monoatomic substituents (slope of the Charton's constants 3.92) than for substituents including more atoms (slope of the Charton's constants 2.09). A small value of the reaction constant ρ⁺ has been elucidated due to the lower conjugation between the reaction centre and the benzene ring as a consequence of the geometric twist of the reaction centre out of the main aromatic plane accompanied by fading mesomeric interaction between the reaction centre and the substituents attached to the benzene ring. The isopropyl group in the carbocation is twisted less out of the aromatic plane for the monoatomic substituents and, therefore, also a small difference in the bulk of substituents has considerable steric influence on the conjugation between the carbocation and the benzene ring bearing substituents. On the contrary, the isopropyl group in the carbocations with polyatomic substituents is twisted to such a degree that changes in the bulk of substituents affect the resonant stabilization negligibly. Similar conclusions were also deduced from the correlations of the substitution constants σ_I and σ_R⁺.

Full text of DOI:10.1135/cccc2008115

ortho-Effect on the Acid-Catalyzed Hydration
85
ortho-EFFECT ON THE ACID-CATALYZED HYDRATION OF
2-SUBSTITUTED α-METHYLSTYRENES
1,
2
3
Ondřej PRUSEK *, Filip BUREŠ and Oldřich PYTELA
Faculty of Chemical Technology, University of Pardubice,
nám. Čs. legií 565, CZ-532 10 Pardubice, Czech Republic;
1
2
3
e-mail: ondrej.prusek@upce.cz, filip.bures@upce.cz, oldrich.pytela@upce.cz
Received May 13, 2008
Accepted Septem ber 4, 2008
Publish ed on lin e Jan uary 27, 2009
Dedicated to the memory of Professor Otto Exner.
α-Meth ylstyren e an d n in e ortho-substituted an alogs h ave been syn th esized an d th e kin etics
of th eir acid-catalyzed h ydration in aqueous solution s of sulfuric acid at 25 °C h ave been in -
vestigated. Th e kin etic acidity fun ction HS h as been con structed from th e depen den ce of th e
observed rate con stan ts kobs on th e sulfuric acid con cen tration . Th e catalytic rate con stan ts
of th e acid-catalyzed h ydration kortho h ave been calculated as well. Th e iden tical sh ape of th e
kin etic acidity fun ction s for ortho- an d para-derivatives con firm s wh at th e con sisten t m ech a-
n ism A-SE2 of th e acid-catalyzed h ydration h as already proved for th e correspon din g para-
derivatives. Th e A-SE2 m ech an ism in volves a rate-determ in in g proton tran sfer of th e h y-
drated proton to th e substrate. From th e depen den ce of th e catalytic rate con stan ts of th e
ortho-derivatives on th e catalytic rate con stan ts of th e para-derivatives, it is seen th at th e
logarith m of th e catalytic rate con stan t for h ydrogen as a substituen t is m arkedly out of th e
ran ge of th e oth er substituen ts an d, sim ultan eously, th at th e ortho-derivatives react sign ifi-
can tly slower th an th e correspon din g para-derivatives. In correlation with th e substiten t
con stan ts σp+, a reaction con stan t of ρ+ = –1.45 h ave been foun d. Th e con stan t is, in abso-
lute value, con siderably sm aller th an th at for para-derivatives (ρ+ = –3.07). In parallel, th e
steric effects are en forced m ore sign ifican tly for th e m on oatom ic substituen ts (slope of th e
Ch arton ’s con stan ts 3.92) th an for substituen ts in cludin g m ore atom s (slope of th e
Ch arton ’s con stan ts 2.09). A sm all value of th e reaction con stan t ρ+ h as been elucidated due
to th e lower con jugation between th e reaction cen tre an d th e ben zen e rin g as a con se-
quen ce of th e geom etric twist of th e reaction cen tre out of th e m ain arom atic plan e accom -
pan ied by fadin g m esom eric in teraction between th e reaction cen tre an d th e substituen ts
attach ed to th e ben zen e rin g. Th e isopropyl group in th e carbocation is twisted less out of
th e arom atic plan e for th e m on oatom ic substituen ts an d, th erefore, also a sm all differen ce
in th e bulk of substituen ts h as con siderable steric in fluen ce on th e con jugation between th e
carbocation an d th e ben zen e rin g bearin g substituen ts. On th e con trary, th e isopropyl group
in th e carbocation s with polyatom ic substituen ts is twisted to such a degree th at ch an ges in
th e bulk of substituen ts affect th e reson an t stabilization n egligibly. Sim ilar con clusion s were
+
also deduced from th e correlation s of th e substitution con stan ts σI an d σR
.
Keyw ord s: Styren e; Acidity fun ction ; Substituen t effects; ortho-Effect; Kin etics; Hydration .
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99
© 2009 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc2008115

86
Prusek, Bureš, Pytela:
Th e study of th e kin etics an d m ech an ism s of th e acid-catalyzed h ydration
of 4-substituted α-m eth ylstyren es based on th e evaluation of kin etic acidity
fun ction s an d substitution effects h as recen tly been reported1. Th e m ech a-
n ism referred to as A-SE2 in volves an addition of th e proton to th e double
bon d of α-m eth ylstyren e an d th e form ation of th e cum yl cation in th e rate-
determ in in g step. As h as been sh own , th e stability of a cum yl cation 1–5
,
or gen erally substituted ben zyl carbocation 2–4,6–8, plays an im portan t role
in th is reaction . Th e stability of such carbocation s is determ in ed by th e
substrate structure an d depen ds in particular on th e substitution at th e
α-position 6,8, th e substitution of th e ben zen e rin g1–4,7,8, an d also on th e sol-
vation . Th e in fluen ce of th e substitution of th e arom atic rin g on th e
carbocation stability is certain ly con siderable. For such reaction s, th e sub-
+
stitution con stan ts σp are th e m ost suitable correlative variables, wh ereas
th e reaction con stan ts ρ+ ran ge from –3.21 to –4.51 (refs1,11–16). Th e reac-
+
tion con stan ts an d th eir depen den ce on th e substitution con stan ts σp in di-
cate a sign ifican t degree of proton tran sfer to th e styren e in th e tran sition
state of th e rate-determ in in g step of th e reaction .
Th e ph ysicoch em ical properties of ortho-substituted α-m eth ylstyren es,
in com parison with th e meta- an d para-substituted an alogs, so far h ave
n ot been system atically in vestigated. Most atten tion h as been paid to th e
2-m eth yl derivatives (UV/Vis 17,18, fluorescen ce19,20, IR 17,21, Ram an 21
NMR 22–24 spectroscopy; kin etics25,26, dipole m om en t27, refractom etry28
basicity in th e gas ph ase29 as well as quan tum -ch em ical calculation s20,21,26
,
,
)
an d less to th e 2-fluoro derivatives (kin etics30,31, dipole m om en t27 an d iso-
tope labelin g32), 2-h ydroxy derivatives (UV/Vis 33 an d IR 33,34 spectroscopy),
2-m eth oxy derivatives (kin etics25,30 an d dipole m om en t27), 2-ch loro deriva-
tives (IR spectroscopy34, kin etics30 an d dipole m om en t27), 2-brom o deriva-
tives, 2-iodo derivatives (dipole m om en t27), an d 2-n itro derivatives (IR
spectroscopy34). All of th e m en tion ed reports im ply th at th e ph ysico-
ch em ical properties of th e ortho-derivatives of th e α-m eth ylstyren e differ
from th ose observed for meta- an d para-derivatives. A size of th e differen ce
depen ds particularly on th e bulkin ess an d structure of th e appen ded sub-
stituen t.
In th e UV/Vis spectra of th e ortho-substituted α-m eth ylstyren es, th e
lon gest-wavelen gth ban d is sh ifted h ypsoch rom ically17,33 wh ereas on e
older report states th at n o absorption ban d appears in th is ran ge18. Th e
IR 17,21,33,34 an d Ram an 21 spectra differ con siderably wh ile th e substitution
effects are fairly seen for th e valen ce vibration νO–H of 2-h ydroxy derivative.
From th e recorded 13C NMR spectra, it h as been sh own th at th e ortho-sub-
stitution in α-m eth ylstyren es ten ds to reduce th e desh ieldin g effect on th e
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99

ortho-Effect on the Acid-Catalyzed Hydration
87
vin yl group at C-1 (ref.22). Th e 13C NMR ch em ical sh ifts of 4- an d 5-sub-
stituted 2-m eth ylcum yl cation s m easured in th e presen ce of SbF5/FSO3H/
SO2ClF at –80 °C correlate sign ifican tly with th e substitution con stan ts.
Wh en com parin g th e reaction con stan ts to oth er derivatives, th e ortho-
m eth yl substitution does n ot affect th e stabilization of th e carbocation . Th e
in fluen ce of th e ortho-substitution is kin etically im portan t in particular for
th ose reaction s in wh ich th e rate of an in term ediate form ation in th e
rate-determ in in g step depen ds on th e stabilization of th e reaction cen tre
th rough reson an ce effects. Wh en com parin g ortho- an d para-derivatives,
th e relative rate of th e dich lorocarben e addition to α-m eth ylstyren e25 de-
crease for th e m eth oxy derivative 5.5 tim es an d for th e para-m eth yl deriva-
tive even 11.7 tim es. Sim ilar relation s were also foun d for th e reaction s
with peroxyl radicals26.
Th e described substitution effects in th e ortho-position of α-m eth yl-
styren es are frequen tly explain ed as a twist of th e double bon d placed in
th e side ch ain from th e m ain arom atic plan e. Th is supposition is furth er
supported by th e observed dipole m om en ts27,28 an d th e steric h in dran ce of
reson an ce, particularly seen in th e UV/Vis spectra17,18,33, in th e m easured
gas-ph ase basicity29 as well as in th e ch em ical reaction s25,26. Th e dih edral
an gle between th e substituted ben zen e rin g an d th e vin yl group estim ated
from th e dipole m om en t of 2-α-dim eth ylstyren e, am oun ts to 71–75° (ref.27).
Quan tum -ch em ical calculation s of th e sam e com poun d give th e dih edral
an gles of 30–60° (ref.20), 112° (C2C1–CαCβ, ref.21), an d 73° (ref.26). Accordin g
to ab in itio calculation s, th e vin yl group is twisted out of th e ben zen e plan e
already for α-m eth ylstyren e (two en ergetic m in im a aroun d 40 an d 140°, re-
spectively) as well as for 2-m eth ylstyren e (two en ergetic m in im a aroun d
150 an d 210°, respectively)35. Even th e styren e itself is n ot a plan ar m ole-
cule36. Th eoretical calculation s predict th e dih edral an gle to be 27°. Th e re-
lated torsion vibration s of th e core-en bon d for ortho- an d meta-substituted
styren es h ave already been reported37
.
Accordin g to th e above statem en ts is it clear th at from th e wh ole spec-
trum of effects referred38–68 to as th e ortho effect, th e acid-catalyzed h y-
dration of 2-substituted α-m eth ylstyren es in volves, in particular, th e twist
of th e isopropen yl group or th e respective cation of th e isopropyl group
from th e ben zen e plan e. Th e correspon din g dih edral an gle depen ds on th e
bulkin ess of th e appen ded substituen t. A twist of th e side group bearin g
th e reaction cen tre affects in particular th e reson an t stabilization of th e
π-electron system , th e m esom eric in teraction between th e ortho-substitu-
en ts an d th e reaction cen tre, an d also th e solvation of th e reaction cen tre.
Th e above-m en tion ed effects will surely h ave differen t im pacts on eith er
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99

88
Prusek, Bureš, Pytela:
th e alken e as a reactan t or on th e carbocation as an in term ediate. Accord-
in g to th e Ham m on d postulate, th e tran sition -state en ergy in th e rate-
determ in in g step is given by th e en ergy of th e carbocation an d, th erefore,
th e rate con stan t will depen d in particular on its stabilization .
With respect to th e specific ch aracter of th e in teraction between th e reac-
tion cen tre an d th e ortho-substituen ts in con crete m olecules an d reaction s,
a quan titative in terpretation of th e ortho-substitution effects seem s to be
difficult. However, two stan dard approach es based on th e sim ilarity prin ci-
ple are already kn own . Th e first, older an d less com m on ly approved ap-
proach in volves th e Ham m ett correlation s in order to propose un iversal
substitution con stan ts σortho (refs42,45). Th e secon d uses com bin ation s of th e
substitution con stan ts describin g th e electron ic effects separately42,69,70
(in ductive or m esom eric), wh ereas a description of th e addition al effects,
in particular th e description of th e steric effects, is realized by addin g oth er
term s to th e correlation equation . Recen tly, quan tum -ch em ical approach es
are also in creasin gly applied for th e description of such experim en tal
data61,62,65
.
From th e above discussion it is clear th at th e substitution effects on th e
acid-catalyzed h ydration of 2-substituted α-m eth ylstyren es can be im -
m en sely com plex an d th eir evaluation an d in terpretation m ay be quite
com plicated. To th e best of our kn owledge, n o effort h as been m ade to
solve th e above problem s an d th us th is topic is th e ch allen ge an d aim of
th is work.
RESULTS AND DISCUSSION
Kinetic Acidity Function
Th e depen den ce of th e observed rate con stan ts kobs for th e acid-catalyzed
h ydration of 2-substituted α-m eth ylstyren es (Sch em e 1) on th e sulfuric acid
con cen tration are sum m arized in Table I. Usin g th ese values, we con -
SCHEME 1
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99

ortho-Effect on the Acid-Catalyzed Hydration
89
structed71 th e kin etic acidity fun ction H (ref.72). Figure 1 depicts th e con -
structed H-fun ction versus th e con cen tration of th e sulfuric acid used, as
well as th e kin etic acidity fun ction for 4-substituted α-m eth ylstyren es
TABLE I
Wavelen gth s λ used for th e kin etic m easurem en ts, n um ber of th e experim en tal m easure-
m en ts n, ran ge of m olar con cen tration s c of catalytic sulfuric acid, th e catalytic rate con -
stan ts log korth o of th e acid-catalyzed h ydration of ortho substituted α-m eth ylstyren es an d
th eir stan dard deviation s sk
Com pd
2-X
λ, n m
n
c, m ol l–1
log korth o
sk
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
254
228
232
238
236
238
252
234
208
246
18
15
14
15
17
17
12
15
13
11
0.65–4.71
2.03–5.70
5.70–8.77
0.40–3.88
0.51–4.16
0.51–4.16
2.51–5.45
2.76–6.67
5.23–8.09
6.18–8.55
–3.842
–4.698
–6.598
–3.317
–3.544
–3.628
–4.624
–5.207
–6.317
–6.602
0.030
0.039
0.024
0.029
0.019
0.029
0.024
0.032
0.026
0.038
CH3
CF3
OH
OCH3
OC2H5
SCH3
F
Cl
1j
Br
FIG. 1
Com parison of th e kin etic acidity fun ction s for 4-substituted (᭺) an d 2-substituted (᭹)
α-m eth ylstyren es, respectively, in aqueous sulfuric acid at 25 °C
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99

90
Prusek, Bureš, Pytela:
obtain ed un der th e sam e reaction con dition s. Th e alm ost iden tical sh ape
of th e depen den ce for both kin etic acidity fun ction s im plies th at th e con -
clusion s m ade for th e A-SE2 (refs73,74) m ech an ism of th e acid-catalyzed
h ydration for para-derivatives1 h old true also for ortho-derivatives. Th e
m ech an ism A-SE2 in volves th e rate-determ in in g tran sfer of a h ydrated pro-
ton to th e substrate – 2-substituted α-m eth ylstyren e.
The Relationship Between ortho- and para-Substitution for α-Methylstyrenes
An an alysis of th e relation sh ip between ortho- an d para-substitution on a
un iform substrate51, in th e sam e reaction an d un der th e sam e con dition s,
seem s to be a proper tool to evaluate th e ortho-effect. An advan tage of th is
approach is its sim ply defin ed ph ysical m odel with out extern al param eters
(substitution con stan ts with un equal reliability). Neverth eless, th e experi-
m en tal errors of both variables (ran dom quan tities) rem ain a lim itation .
Th e relation sh ip between logarith m s of both catalytic rate con stan ts of th e
acid-catalyzed h ydration of th e ortho- an d para-substituted α-m eth yl-
styren es is illustrated in Fig. 2. Th is picture dem on strates th at th e logarith m
of th e catalytic rate con stan t for h ydrogen as a substituen t is m arkedly out
of th e ran ge of th e oth er substituen ts an d, sim ultan eously, th at th e ortho-
FIG. 2
Relation sh ip between th e logarith m s of th e catalytic rate con stan ts of th e acid-catalyzed
h ydration of 2-substituted (log kortho) an d 4-substituted (log kpara) α-m eth ylstyren es in aqueous
sulfuric acid at 25 °C. Th e poin ts except h ydrogen are fitted by weigh ted lin ear regression with
m arked 95% con fiden ce region th e regression lin e
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ortho-Effect on the Acid-Catalyzed Hydration
91
derivatives react sign ifican tly slower th an th e correspon din g para-deriva-
tives. Th e apparen tly in h om ogen eous results are m ost likely caused by th e
superposition of m an y factors, wh ich affect both th e reactan t an d also pre-
dom in an tly th e carbocation form ed with in th e reaction . Th e followin g
factors are probably th e m ost crucial on es: (i) a decrease in th e con jugation
between th e reaction cen tre an d th e ben zen e rin g caused by th e geom etric
twist of th e reaction cen tre from th e ben zen e plan e, (ii) a ch an ge in th e
m esom eric in teraction of th e reaction cen tre an d th e substituen t depen din g
in particular on th e exten t of such a twist, (iii) steric h in dran ce preven tin g
th e access of th e reagen t to th e reaction cen tre, (iv) steric h in dran ce of th e
solvation stabilization of th e carbocation evolvin g in th e rate-determ in in g
step of th e reaction , (v) specific in teraction s of th e reaction cen tre with th e
substituen t. Th e weigh ted lin ear regression of logarith m s of th e catalytic
rate con stan ts for ortho-substituted α-m eth ylstyren es (excludin g outliers for
h ydrogen ) on th e logarith m s of catalytic rate con stan ts for para-derivatives
an d on Ch arton ’s steric con stan ts υ (ref.43) provided th e followin g relation -
sh ip (1)
log kortho = –(2.0 ± 0.3) + (0.91 ± 0.09) log kpara
n = 9, s = 0.375, R = 0.964, F(1,7) = 92.4 .
(1)
Th e regression coefficien t for Ch arton ’s steric con stan ts was statistically n ot
sign ifican t an d, th erefore, it is n ot stated in Eq. (1). On th e oth er h an d,
from th e statistical in sign ifican ce of th e regression coefficien t for th e con -
stan ts υ, we can n ot deduce th at steric effects were n ot in volved. Th e outlier
log kortho for th e m on atom ic substituen t – h ydrogen an d th e fron tier value
log kortho for Br as a substituen t on th e oth er side of th e 95% con fiden ce
region of th e regression lin e (Fig. 2) stron gly in dicate th e sign ifican ce of
steric effects. Sin ce ortho-substitution in volves a wide ran ge of th e above-
m en tion ed factors, th e steric effects in Eq. (1) could n ot be sim ply described
by addin g th e steric con stan ts υ or oth er related con stan ts to th e correla-
tion relation sh ip.
+
Interpretation of ortho-Substitution Through the Constants σp
+
Th e substitution con stan ts σp (refs3,4,75) are best suited1 for a quan titative
description of th e substitution effects in th e reaction s in volvin g carbo-
cation s as in term ediates. Figure 3 illustrates th e depen den ce of logarith m s
of th e catalytic rate con stan ts of th e acid-catalyzed h ydration for 2-sub-
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99

92
Prusek, Bureš, Pytela:
stituted α-m eth ylstyren es on th e substitution con stan ts σp+. Th e relation -
sh ips depicted in Figs 2 an d 3 correspon d to each oth er – with th e
h ydrogen substituen t as an outlier, wh ereas th e Br an d CH3S substituen ts
lie with in th e lim its of th e con fiden ce region of th e regression lin e. Th e
lin ear regression of logarith m s of th e catalytic rate con stan ts for ortho-sub-
stituted α-m eth ylstyren es on th e substitution con stan ts σp+, in cludin g th e
values for h ydrogen , provided th e followin g relation sh ip (2)
+
log kortho = –(5.45 ± 0.26) – (2.28 ± 0.48)σp
n = 10, s = 0.702, R = 0.859, F(1,8) = 22.5
(2)
an d relation sh ip (3) excludin g th e h ydrogen values
+
log kortho = –(5.70 ± 0.15) – (2.52 ± 0.26)σp
(3)
n = 9, s = 0.373, R = 0.965, F(1,7) = 93.4 .
In com parison with th e correspon din g relation sh ip for th e para-deriva-
tives1, th e relation sh ips in Eqs (2) an d (3) are n ot as close (para: s = 0.242,
R = 0.990). Th e reaction con stan t in its absolute value is sm aller for
FIG. 3
Depen den ce of th e logarith m s of th e catalytic rate con stan ts of th e acid-catalyzed h ydration
+
for 2-substituted α-m eth ylstyren es log kortho on th e substitution con stan ts σp in aqueous sul-
furic acid at 25 °C. Th e poin ts except h ydrogen are fitted by weigh ted lin ear regression with
m arked 95% con fiden ce region th e regression lin e
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ortho-Effect on the Acid-Catalyzed Hydration
93
ortho-derivatives (para: ρ+ = –3.07). Th is im plies th at th e substituen t effects
are n ot perfectly described an d th at th e in fluen ce of th e ortho-substitution
is lower th an th at for th e para-position . However, an in clusion of th e steric
con stan ts υ in to Eq. (2) leads to a tigh ter relation sh ip (4)
+
log kortho = –(4.34 ± 0.41) – (1.90 ± 0.36)σp – (2.14 ± 0.71)υ
(4)
n = 10, s = 0.494, R = 0.942, F(2,7) = 27.3 .
Th e regression coefficien t for th e steric con stan t υ is, in con trast to Eq. (1),
statistically sign ifican t. Its large n egative value (e.g. th e steric con stan t for
th e alkalin e h ydrolysis of ph en yl-2-substituted ben zoates76 am oun ts to 1.4)
in dicates an im portan t steric retardation of th e reaction as a con sequen ce
of th e steric effects. Th e reaction con stan t ρ+ is sm aller in com parison with
Eqs (2) an d (3), respectively. Th e large residual stan dard deviation s an d, on
th e con trary, th e little explain ed variability (100R2 = 89%) h in der a relevan t
ph ysicoch em ical in terpretation of th e obtain ed relation sh ip. Hen ce, a sys-
tem atic an alysis was perform ed in order to extract th e statistically m ost
accurate explan atory variables based on th e substitution con stan ts. Th e fol-
lowin g relation sh ip h as been foun d (5)
+
log kortho = –(3.97 ± 0.16) – (1.45 ± 0.15)σp
–
– (3.92 ± 0.38)υ(1) – (2.09 ± 0.26)υ(>1)
n = 10, s = 0.186, R = 0.993, F(3,6) = 144
(5)
wh ere th e variables υ(1) an d υ(>1) refer to Ch arton ’s steric con stan t for th e
m on atom ic an d polyatom ic substituen ts (for oth ers 0), respectively. Havin g
statistically sign ifican t regression coefficien ts, n o outliers, an d n orm al resi-
due distribution , Eq. (5) is also statistically valid. Th e residual stan dard de-
viation s is even sm aller th an th ose for th e para-substitution (see above).
Th e sm all reaction con stan t ρ+ (e.g. com pare with th e followin g data4 for
para-substitution : styren e, H2O–H2SO4, ρ+ = –3.69, s = 0.21; α-CF3-styren e,
H2O–H2SO4, ρ+ = –5.36, s = 0.176; α-MeO-styren e, H2O–H2SO4, ρ+ = –2.26,
s = 0.118 an d also refs11–16) im plies th at in teraction in ortho-derivatives
between th e reaction cen tre an d th e substituen t is sign ifican tly decreased
com pared to th ose observed for para-substitution . Th is could be explain ed
due to a lower degree of con jugation between th e reaction cen tre an d th e
ben zen e rin g as a con sequen ce of th e geom etric twist of th e reaction cen tre
out of th e m ain arom atic plan e, accom pan ied by th e van ish in g of th e
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94
Prusek, Bureš, Pytela:
m esom eric in teraction between th e reaction cen tre an d th e substituen t, de-
pen din g on th e exten t of such a distortion . Regression coefficien ts for υ(1)
an d υ(>1) both h ave n egative sign s, h en ce th e catalytic rate con stan t de-
creases with th e in creasin g bulkin ess of substituen t. Th e regression coeffi-
cien t for υ(1) in Eq. (5) is alm ost five-tim es h igh er th an th ose for υ(>1). Th is
furth er im plies th at th e m on oatom ic substituen ts affect th e rate con stan t
m ore con siderably th an th e polyatom ic on es. Th is is m ost likely due to a
sm all twist of th e isopropyl group in th e carbocation gen erated from th e
m on oatom ic-substituted α-m eth ylstyren es, wh ere even sm all differen ces in
th e n ature of substituen ts distin ctively affect th e en tire con jugation between
th e carbocation an d th e substituen ts attach ed to th e ben zen e rin g. On th e
con trary, th e isopropyl groups in th e polyatom ic-substituted α-m eth yl-
styren es are twisted to such an exten t th at ch an ges in th e bulkin ess of th e
substituen ts affect th e reson an ce stabilization to a n egligible exten t.
+
Interpretation of ortho-Substitution Through the Constants σI and σR
+
Th e relation sh ip of log kortho on th e substitution con stan ts σI an d σR in -
cludin g th e steric con stan ts υ(1) an d υ(>1) is given by Eq. (6)
+
log kortho = –(3.93 ± 0.21) – (2.25 ± 0.67)σI – (1.51 ± 0.20)σR
– (3.67 ± 0.63)υ(1) – (2.00 ± 0.36)υ(>1)
–
(6)
n = 10, s = 0.233, R = 0.991, F(4,5) = 68.2 .
Wh en com parin g Eq. (6) with (5), relation sh ip (6) is m uch less tigh ter
wh ereas regression coefficien ts for th e variables υ(1) an d υ(>1) are con sisten t
h avin g an alogical in terpretation as for Eq. (5). Wh en com parin g Eq. (6)
with equation obtain ed for para-substitution 1, both regression s are statisti-
+
cally sim ilar wh ereas th e reaction con stan ts ρI an d ρR for ortho-substitution
+
are rough ly h alf-size (para: s = 0.227, R = 0.992, ρI = –4.16, ρR = –2.94), an d
+
th e reaction con stan t ρR h as ch an ged sligh tly m ore th an ρI.
A system atic an alysis of th e statistically m ost accurate explan atory vari-
+
ables based on th e substitution con stan ts σI an d σR provided an even sta-
tistically tigh ter relation sh ip (7)
log kortho = –(3.82 ± 0.17) – (3.02 ± 0.59)σI – (1.53 ± 0.16)σR+(con jug) –
– (3.21 ± 0.55)υ(1) – (1.76 ± 0.31)υ(>1)
n = 10, s = 0.192, R = 0.994, F(4,5) = 101
(7)
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99

ortho-Effect on the Acid-Catalyzed Hydration
95
+
wh ere σR+(con jug) is equal to σR for th e con jugatin g substituen ts an d 0 for
th e oth ers (H, CH3, CF3). Th e reason for such selection m ay be seen in an
+
overestim ated value of σR for th e substituen t CH3 (–0.29, ref.68) in Eq. (6).
+
It is also worth wh ile to n otice th at th e reaction con stan t ρR alm ost did n ot
ch an ge, wh ereas th e reaction con stan t ρI in creased. Wh en com parin g th e
+
absolute values of ρI an d ρR con stan ts for ortho- an d para-substitution s,
+
ρI an d ρR values for th e ortho-substitution are lower with in a factor of on e-
th ird an d on e-h alf, respectively. Th is is un am biguous eviden ce th at th e
ortho-substitution of th e acid-catalyzed h ydrolysis of α-m eth ylstyren es acts
as a steric h in dran ce-factor, affectin g in particular, th e reson an t stabiliza-
tion of th e carbocation .
EXPERIMENTAL
1H NMR spectra were recorded in CDCl3 (10% solution s) at 360 MHz with a Bruker AMX
360 in strum en t at 25 °C. Ch em ical sh ifts are reported in ppm relative to th e sign al of HMDS
(0.05 ppm ). Couplin g con stan ts (J) are given in Hz. Th e particular proton s are m arked as fol-
lows (X = ortho-substituen t).
Preparation of ortho-Substituted α-Meth ylstyren es. Gen eral Meth od
Th e gen eral m eth od in volves an addition of Grign ard reagen ts to th e appropriate carbon yl
com poun ds (keton es, esters, an d acyl ch lorides). Th e eth ereal solution of th e substrate was
added dropwise to a stirred solution of th e Grign ard reagen t (3 equiv.) in eth er over th e pe-
riod of 1 h at 25 °C. Th e reaction m ixture was refluxed for an addition al 2 h , cooled an d
poured on ice. Upon acidification with sulfuric acid, th e organ ic ph ase was separated,
wash ed with Na2SO3 (10% aqueous solution ) an d water, dried (Na2SO4), an d th e solven t
evaporated. Th e crude alcoh ol was purified by vacuum distillation accom pan ied by eith er
spon tan eous or P2O5-in duced deh ydration . Th is protocol provide a straigh tforward an d gen -
eral approach to th e target com poun ds with sim ple m eth odology an d easy work-up. No at-
tem pts were un dertaken to furth er optim ize th e preparative yields.
α-Methylstyrene (1a) was syn th esized from ben zoyl ch loride an d m eth ylm agn esium iodide
followin g th e gen eral procedure an d purified by vacuum distillation with added P2O5. Yield
20
20
41%, b.p. 48 °C/14 m bar (ref.25, b.p. 57 °C/13 m bar), nD = 1.5342 (ref.25, nD = 1.5330).
1H NMR (360 MHz, CDCl3): 7.44 d, 2 H, 3J = 9.0 (H-2,6); 7.30 t, 2 H, 3J = 9.0 (H-3,5); 7.24 t,
1 H, 3J = 9.0 (H-4); 5.34 s, 1 H (H-8); 5.05 s, 1 H (H-9); 2.09 s, 3 H (H-7).
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99

96
Prusek, Bureš, Pytela:
2-Methyl-α-methylstyrene (1b ) was syn th esized from aceton e an d 2-m eth ylph en yl-
m agn esium brom ide followin g th e gen eral procedure an d purified by vacuum distillation
with added P2O5. Yield 10%, b.p. 47–50 °C/11 m bar (ref.17, b.p. 172–173 °C/760 m bar),
20
20
nD
= 1.5147 (ref.17, nD
= 1.5152). 1H NMR (360 MHz, CDCl3): 7.08–7.15 m , 4 H
(H-3,4,5,6); 5.16 s, 1 H (H-8); 4.82 s, 1 H (H-9); 2.29 s, 3 H (2-CH3); 2.01 s, 3 H (H-7).
2-Trifluoromethyl-α-methylstyrene (1c) was syn th esized from 2-(trifluorom eth yl)ben zoyl
ch loride an d m eth ylm agn esium iodide followin g th e gen eral procedure an d purified by
20
vacuum distillation with added P2O5. Yield 9%, b.p. 31 °C/6 m bar, nD = 1.4512. 1H NMR
(360 MHz, CDCl3): 7.60 d, 1 H, 3J = 8.1 (H-3); 7.42 t, 1 H, 3J = 8.1 (H-5); 7.29 t, 1 H, 3J = 8.1
(H-4); 7.19 d, 1 H, 3J = 8.1 (H-6); 5.17 s, 1 H (H-8); 4.84 s, 1 H (H-9); 2.03 s, 3 H (H-7).
2-Hydroxy-α-methylstyrene (1d ) was syn th esized from 2-h ydroxyacetoph en on e an d m eth yl-
m agn esium ch loride in THF followin g th e gen eral procedure an d purified by vacuum distil-
lation with spon tan eous deh ydration . Yield 63%, b.p. 55 °C/1 m bar (ref.33, b.p. 92–93 °C/
20
20
16 m bar), nD = 1.5446 (ref.33, nD = 1.5463). 1H NMR (360 MHz, CDCl3): 8.20 s, 1 H
(2-OH); 7.65 d, 1 H, 3J = 7.8 (H-3); 7.24 t, 1 H, 3J = 7.8 (H-5); 7.11 d, 1 H, 3J = 7.8 (H-6);
7.01 t, 1 H, 3J = 7.8 (H-4); 5.32 s, 1 H (H-8); 5.09 s, 1 H (H-9); 2.06 s, 3 H (H-7).
2-Methoxy-α-methylstyrene (1e) was syn th esized from m eth yl 2-m eth oxyben zoate an d
m eth ylm agn esium iodide followin g th e gen eral procedure an d purified by vacuum distilla-
tion with spon tan eous deh ydration . Yield 45%, b.p. 77–79 °C/2–3 m bar (ref.27, b.p. 56–60 °C/
20
20
1 m bar), nD = 1.5338 (ref.27, nD = 1.5296). 1H NMR (360 MHz, CDCl3): 7.15–7.21 m , 2 H
(H-3,5); 6.83–6.89 m , 2 H (H-4,6); 5.13 s, 1 H (H-8); 5.04 s, 1 H (H-9); 3.80 s, 3 H (2-OCH3);
2.10 s, 3 H (H-7).
2-Ethoxy-α-methylstyrene (1f) was syn th esized from eth yl 2-eth oxyben zoate an d m eth yl-
m agn esium iodide followin g th e gen eral procedure an d purified by vacuum distillation with
20
spon tan eous deh ydration . Yield 22%, b.p. 55 °C/4 m bar, nD = 1.5227. 1H NMR (360 MHz,
CDCl3): 7.16–7.22 m , 2 H (H-3,5); 6.83–6.89 m , 2 H (H-4,6); 5.09 s, 1 H (H-8); 5.05 s, 1 H
(H-9); 4.02 q, 2 H, 3J = 7.8 (2-OCH2CH3); 1.57 s, 3
(2-OCH2CH3).
H
(H-7); 1.38 t, 3 H, 3J = 7.8
2-Methylthio-α-methylstyrene (1g) was syn th esized from m eth yl 2-(m eth ylth io)ben zoate
an d m eth ylm agn esium iodide followin g th e gen eral procedure an d purified by vacuum dis-
20
tillation with spon tan eous deh ydration . Yield 20%, b.p. 98 °C/12 m bar, nD
= 1.5781.
1H NMR (360 MHz, CDCl3): 7.15–7.23 m , 2 H (H-3,5); 7.06–7.09 m , 2 H (H-4,6); 5.23 s, 1 H
(H-8); 4.94 s, 1 H (H-9); 2.40 s, 3 H (H-7); 2.08 s, 3 H (2-SCH3).
2-Fluoro-α-methylstyrene (1h ) was syn th esized from 2-fluoroben zoyl ch loride an d m eth yl-
m agn esium iodide followin g th e gen eral procedure an d purified by vacuum distillation with
20
added P2O5. Yield 23%, b.p. 49 °C/21 m bar (ref.27, b.p. 62 °C/28 m bar), nD = 1.5059 (ref.27
,
25
nD = 1.5031). 1H NMR (360 MHz, CDCl3): 7.31 t, 1 H, 3J = 7.6 (H-5); 7.22–7.27 m , 1 H
(H-3); 7.10 d, 1 H, 3J = 7.5 (H-6); 7.01–7.06 m , 1 H (H-4); 5.24 s, 1 H (H-8); 5.04 s, 1 H (H-9);
2.16 s, 3 H (H-7).
2-Chloro-α-methylstyrene (1i) was syn th esized from 2-ch loroben zoyl ch loride an d m eth yl-
m agn esium iodide followin g th e gen eral procedure an d purified by vacuum distillation with
20
added P2O5. Yield 21%, b.p. 39–40 °C/5 m bar (ref.30, b.p. 75 °C/14 m bar), nD = 1.5337
25
(ref.30, nD = 1.5329). 1H NMR (360 MHz, CDCl3): 7.30 d, 1 H, 3J = 7.6 (H-3); 7.11–7.28 m ,
3 H (H-4,5,6); 5.20 s, 1 H (H-8); 4.94 s, 1 H (H-9); 2.07 s, 3 H (H-7).
2-Bromo-α-methylstyrene (1j) was syn th esized from 2-brom oben zoyl ch loride an d m eth yl-
m agn esium iodide followin g th e gen eral procedure an d purified by vacuum distillation with
20
added P2O5. Yield 30%, b.p. 56–57 °C/4 m bar (ref.27, b.p. 55–65 °C/0.9 m bar), nD = 1.5576
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 85–99

ortho-Effect on the Acid-Catalyzed Hydration
97
20
(ref.27, nD = 1.5530). 1H NMR (360 MHz, CDCl3): 7.49 d, 1 H, 3J = 8.0 (H-3); 7.20 t, 1 H,
3J = 7.6 (H-5); 7.15 d, 1 H, 3J = 7.6 (H-6); 7.06 t, 1 H, 3J = 7.6 (H-4); 5.18 s, 1 H (H-8); 4.89 s,
1 H (H-9); 2.05 s, 3 H (H-7).
Kin etic Measurem en ts
A solution of respective α-m eth ylstyren es (2–5 µl) in m eth an ol was added to a cell con tain -
in g 2 m l of aqueous sulfuric acid (c = 0.017–9.58 m ol l–1) kept at 25 ± 0.1 °C. Th e cell con -
ten t was m ixed, an d th e absorban ce decrease was m on itored spectroph otom etrically (UV/Vis
spectroph otom eter HP 8452A) at suitable wavelen gth s (Table I) for a period of at least 5 h alf-
lives. Th e kin etic depen den cies obtain ed were treated by a kn own algorith m 77 to calculate
th e observed rate con stan ts kobs
.
Con struction of th e Kin etic Acidity Fun ction
Th e obtain ed depen den cies of th e logarith m observed rate con stan ts log kobs on th e sulfuric
acid con cen tration were treated by a kn own algorith m to con struct th e kin etic acidity fun c-
tion 71. Likewise, th e catalytic rate con stan ts log kortho were obtain ed th is way.
Correlation Valuation
Th e substitution con stan ts used were taken from th e literature43,69. Th e depen den ce of loga-
rith m s of th e catalytic rate con stan ts log kortho on substitution con stan ts were exam in ed by
m ultivariate graph ical display m eth ods an d subsequen tly treated by m ultiple lin ear regres-
sion s (in cludin g t-test, F-test, assessin g m ulticollin earity, an d residual an alysis). Residuals in
all of th e presen ted regression s h ad n orm al distribution an d outliers were n ot detected. Th e
OPstat Program 78 was em ployed for all statistical calculation s.
This work was supported by the Ministry of Education, Youth and Sport of the Czech Republic
(MSM 0021627501).
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