Reacting Electrophile in Acylation Reactions
J. Am. Chem. Soc., Vol. 118, No. 50, 1996 12579
was determined using spectra at the end of reaction (conversion >98%)
as a reference. From the known extinction coefficient and the measured
path length d36 the concentration of 11b′ was calculated. In order to
obtain second-order rate constants in presence of 13 velocities V were
calculated from concentration-time data averaged before and after the
specified time. The slope of the plot V versus the product of
concentration of 11b′ and aromatic (calculated from concentration-time
data) corresponds to kbobs. In presence of HOTf the second-order rate
constants were determined from the integrated rate law given in the
literature.37
IR Extinction Coefficient of 11b′. Aliquots of a stock solution of
11b (c ) 0.172 ( 5 M) in DCE were mixed with the same volume of
a solution of HOTf (0.402 M) in DCE. The mixtures were diluted to
a known volume, and the IR spectra were recorded. The extinction
was calculated from the difference to a solution of 13 and HOTf in
DCE in order to rule out weak hydrogen bond absorptions between ν
) 2200-2400 cm-1. The values reveal good linearity for concentra-
tions up to 0.039 M (R ) 0.9996, 6 points).
Figure 9. Second-order kinetics of acylations of 2e with 11b′.
Gas Chromatography. Samples (0.5 or 1 mL) were mixed with
methanol (1 mL) and if necessary with 1 mL of a solution of the internal
standard 1,3-dinitrobenzene (competitive conversions) or 13 (kinetic
studies in presence of HOTf). After 1 h the mixture was extracted
with 1 mL of aqueous Na2CO3 solution (5%). The aqueous phase was
extracted twice with DCE (1 mL), and the combined extracts were dried
(MgSO4), filtered, and used for GC analysis.
recrystallization from chloroform/hexane: 21.3 g (72%) colorless
crystals, mp 136 °C. From Mg (5.7 g, 0.235 mol) in THF (50 mL),
bromide of 10b (63.3 g, 0.222 mol) in THF (120 mL) and CO2 (500 g,
11.4 mmol) in THF (500 mL); yield after recrystallization from
chloroform/petroleum ether: 44.6 g (81%) colorless crystals, mp 186
°C.
(c) Chlorination of acids to acid chlorides was carried out by
refluxing in thionyl chloride for 3 h and subsequent distillation; from
acid of 10a (10 g, 45 mmol) in 20 mL of thionyl chloride; yield: 10
g (91%) colorless solidifying oil, bp 88 °C/0.05 Torr. From acid of
10b (6.5 g, 26 mmol) in 20 mL of thionyl chloride; yield: 6.5 g (93%)
colorless solidifying oil, bp 104-106 °C/0.0005 Torr, mp 62.5 °C.
(d) 11a was prepared as described below from 4-(2,2-dimethylprop-
oxy)methylbenzoyl chloride (0.893 g, 3.7 mmol) in 10 mL of DCE
and AgOSO2CF3 (AgOTf)23d (0.952 g, 3.7 mmol) in 10 mL of DCE
but decomposed after workup.
In case of 11b, AgOTf (0.82 g, 3.2 mmol) was added at 0 °C
portionwise to a stirred solution of 4-(2,2-dimethylpropoxy)-2,3,5-
trimethylbenzoyl chloride (0.78 g, 2.9 mmol) in 1,1,2-trichlorotrifluo-
roethane (15 mL). After stirring at 0 °C for 1 h in the absence of light
precipitated AgCl was filtered off, and the filtrate was concentrated by
removal of the solvent in Vacuo. Removal of solvent traces in Vacuo
at 0.001 Torr (6 h) yielded 1.10 g (99%) 11b as brown oil. Data see
Table 3.
Methyl 5-(4-(2,2-Dimethylpropoxy)-2-methylbenzoyl)-4-(2,2-di-
methylpropoxy)-2-methylbenzoate (12). A solution of 11a [prepared
from AgOTf (0.952 g) and acid chloride (0.893 g)] was allowed to
stand at room temperature for 2 h before mixing with 50 mL of
methanol. After aqueous workup23c the mixture was chromatographed
on silica gel with petroleum ether/ethyl acetate (15:1) to yield 0.05 g
(6%) 12.
Absolute concentrations were calculated from the measured integrals
of separated compounds using specific responce factors38 for methyl
esters and/or products relative to the used internal standards.
Preparation of Ketones 14b-d. At -15 °C 10b (2.06 g, 10 mmol)
was added dropwise to a stirred solution of 4-, 3-, or 2-methylbenzoyl
chloride39 (1.6 g, 10 mmol) and FeCl3 (1.6 g, 10 mmol) in 10 mL of
DCE. After stirring for a further 3 h at 0 °C the reaction mixture was
hydrolyzed with 20 g of ice, stirred for 1 h, and extracted three times
with dichloromethane (20 mL each). The combined extracts were
washed with aqueous NaOH (5%) and water and dried (MgSO4), and
the solvent was removed in Vacuo. 14b and 14c were recrystallized
from n-hexane; yield of colorless crystals: 2.41 g (74%) 14b, mp 97
°C; 2.20 g (68%) 14c, mp 88 °C. 14d was chromatographed on silica
gel with petroleum ether/dichloromethane (1:1); yield: 2.1 g (65%) as
colorless oil. Data see Table 3.
Acknowledgment. Dedicated to Professor Rolf Gleiter on
the occasion of his 60th birthday. This work was supported by
the Fonds der Chemischen Industrie.
JA9624331
(28) Gutmann, R. Dissertation, Universita¨t Stuttgart, 1981.
(29) Dimroth, K.; Mach, W. Angew. Chem., Int. Ed. Engl. 1968, 7, 460-
461.
Solutions of triflates were prepared at room temperature in DCE
either by weighing (distillable compounds) or by adding a solution of
the corresponding acid chloride in 10 mL DCE to a stirred suspension
of AgOTf (1.1 equiv) in 10 mL of DCE. After 0.5 h precipitated AgCl
was filtered off and washed with 2 mL of DCE. The combined filtrates
were transferred to a 25 mL graduated flask under Ar atmosphere and
filled up with DCE. The concentration was determined by GC from
at least two samples.
(30) (a) Epple, G. Dissertation, Universita¨t Stuttgart, 1972. (b) Carruthers,
W.; Stewart, H. N. M.; Hansell, P. G.; Kelly, K. M. J. Chem. Soc. C 1967,
2607-2613. (c) Gore, P. H.; Hoskins, J. A. J. Chem. Soc. C 1970, 517-
522. (d) Coops, J.; Nauta, W. Th.; Ernsting, M. J. E.; Faber, A. C. Recl.
TraV. Chim. Pays-Bas 1940, 59, 1109-1116. (e) Fuson, R. C.; Gaertner,
R. J. Org. Chem. 1948, 13, 496-501. (f) de Roos, A. M. Recl. TraV. Chim.
Pays-Bas 1968, 87, 1359-1367 and 1381-1386. (g) Jones, B. J. Chem.
Soc. 1936, 1854-1862. (h) Hamacher, H. Arch. Pharm. 1975, 308, 290-
301.
For competitive conversions either 10 mL of a solution of one
aromatic (0.04 M) in DCE was mixed at room temperature with 40
mL of a solution of two triflates (1:1, each ca. 0.025 M, exact ratio
determined by GC) in DCE or 30 mL of a solution of two aromatics
(each 0.33 M) in DCE were mixed with 20 mL of a solution of triflate
(ca. 0.05 M) in DCE. The samples taken in the course of reaction
were determined by GC.
Kinetic Measurements. To 22 mL of a solution of 11b (c ) 61.6-
208.8 mM) in DCE containing HOTf or base 13 in a 25 mL graduated
Schlenk flask, standing at 25 ( 0.2 °C for 1 h, the aromatic was added,
the flask was filled up with DCE, and the reaction was started by
shaking. Samples were taken via syringe at different times for
derivatization and GC analysis and in the presence of 13 just after that
additionally for IR measurements. The extinction at ν ) 2188 cm-1
(31) (a) Goering, H. L.; Rubin, T.; Newman, M. S. J. Am. Chem. Soc.
1954, 76, 787-791. (b) Grundy, J.; James, B. G.; Pattenden, G. Tetrahedron
Lett. 1972, 757-758.
(32) Danre´e, B.; Seyden-Penne, J. Bull. Soc. Chim. France 1967, 415.
(33) Haszeldine, R. N.; Kidd, J. M. J. Chem. Soc. 1954, 4228-4232.
(34) Beilsteins Handbuch der organischen Chemie; vol. 6, 3rd supple-
ment; Springer: Berlin, 1966; p 1321.
(35) Hussey, A. S. J. Am. Chem. Soc. 1951, 73, 1364-1365.
(36) Weitkamp, H.; Barth, R. Einfu¨hrung in die quantitatiVe Infrarot-
spektrometrie; Thieme: Stuttgart, 1976.
(37) Bunnett, J. F. In Techniques of Chemistry, 4th ed.; Bernasconi, C.
F., Ed.; Wiley: New York, 1986; Vol. VI, part 1, pp 183-185.
(38) Schomburg, G. Gaschromatographie: Grundlagen, Praxis, Kapil-
lartechnik, 2nd ed.; Verlag Chemie: Weinheim, 1987; pp 62-72.
(39) Organikum, 19th ed.; Becker, H. G. O., Ed.; Verlag der Wissen-
schaften: Berlin, 1993; pp 440-441.