4′-Substituted-4-biphenylyloxenium Ions
at each wavelength were averaged. Product yields were monitored
by HPLC on the same solutions used for kinetics. HPLC conditions
were the following: 20 µL injections on a 4.7 mm × 250 mm C-8
column, 60/40 MeOH/H2O eluent, 1.0 mL/min flow rate, UV
detection at 240 nm. Procedures for fitting product yield data to
the standard “azide clock” equations have been published.9 Similar
procedures were used to fit the product data for 4d and 5d to eqs
2 and 3, respectively.
precursors 2e′ and 2f′ is then enforced by the short lifetimes of
the ions. It remains to be determined if this trapping reaction is
a truly concerted SN2′ process, or an azide-assisted ionization
with trapping proceeding within a short-lived ion sandwich.
Experimental Section
Synthesis. The esters 2c-e, 2e′, and 2f′ were synthesized by
oxidation of the 4′-substituted-4-hydroxybiphenyls with PIDA in
acetic acid or in dichloroacetic acid. The 4′-substituted-4-hydroxy-
biphenyls were purchased (4′-Br, 4′-CN) or made by a Suzuki
coupling procedure (4′-MeO, 4′-Me) or by nitration followed by
hydrolysis of 4-(benzoyloxy)biphenyl (4′-NO2).14a,22 Detailed pro-
cedures for the oxidation have been published elsewhere.8,9 Crude
reaction products were subjected to chromatography on a chro-
matatron (2 mm silica gel, 25/75 to 50/50 EtOAc/hexanes eluent).
Final purification was accomplished by recrystallization from
EtOAc/hexanes (2c-e, 2e′), or further chromatography on the
chromatatron (2f′, 50/50 EtOAc/hexanes). Characterization of each
compound is presented in the Supporting Information.
The sulfonamides 3b and 3c were generated from the corre-
sponding 4′-substituted-4-hydroxybiphenyls14a by amination of the
phenoxide with O-mesitylenesulfonylhydroxylamine in DMF,14b,15
followed by treatment of the resulting hydroxylamine with meth-
anesulfonyl chloride in pyridine.12 Details of the amination and
sulfonylation procedures, as well as purification and characterization
of 3b, 3c, and their precursors O-(4-(4′-methoxyphenyl)phenyl)-
hydroxylamine and O-(4-(4′-methylphenyl)phenyl)hydroxylamine,
are described in the Supporting Information.
Authentic samples of the quinols 4b-f were made by oxidation
of the corresponding 4-hydroxybiphenyls with PIDA in 50/50 CH3-
CN/H2O as previously described for 4a.8 Each quinol was purified
by chromatography on a chromatatron (2 mm silical gel, 50/50
EtOAc/hexanes) followed by recrystallization from EtOAc/hexanes.
Characterization is provided in the Supporting Information. An
authentic sample of the bromo-adduct 6b was made by bromination
of 4-hydroxy-4′-methoxybiphenyl14a with bromine in CHCl3.23 The
azide adducts 5b-f were isolated from reaction mixtures by a
method similar to that described for 5a.8 Briefly, The ester 2c or
2d or sulfonamide 3b (0.20 mmol), dissolved in 2 mL of CH3CN,
was added in 200 µL aliquots every half-life as determined by the
reaction kinetics (below) to 100 mL of a 0.02 M phosphate buffer
(5 vol % CH3CN-H2O, pH 7.0, µ ) 0.5 (NaClO4)) containing 0.2
M NaN3 that was incubated in the dark at 30 °C. After the last
addition, the mixture was incubated in the dark at 30 °C for an
additional 10 half-lives. After cooling in an ice-water bath, the
reaction mixture was extracted with CH2Cl2 (4 × 25 mL). After
drying over Na2SO4, the extract was evaporated to dryness and the
residue was purified by chromatography on a chromatatron (2 mm
silica gel, CH2Cl2 eluent). A similar procedure was followed for
2e′ and 2f′ except that 100 mL of a 0.2 M azide buffer (5 vol %
CH3CN-H2O, pH 4.6, µ ) 0.5 (NaClO4)) was utilized as the
reaction medium. Characterization of the azide adducts is provided
in the Supporting Information.
18O Labeling Experiments. Details for preparing solutions are
found elsewhere.9 A 2.5 µL volume of a 0.02 M solution of 4e or
4f or a 0.04 M solution of 2e′ or 2f′ in CH3CN was injected into
500 µL of a 25 atom % pH 4.6 acetate buffer preincubated at 30
°C. After 1 half-life of the hydrolysis reaction (1800 s for 4e and
2e′, 2700 s for 4f and 2f′) the reaction mixture was cooled in an
ice-water bath and analyzed by LC/MS, using triplicate injections.
LC conditions were the following: 4.6 mm × 250 mm C-8 column,
60/40 MeOH/H2O (0.1% HOAc), 1 mL/min, 20 µL injection,
retention time for 4e ca. 4.2 min, and for 4f ca. 5 min. Control
experiments for 4e and 4f in normal isotopic distribution reaction
solutions were also performed. Mass spectra were obtained on an
ion trap instrument. The electrospray ionization source (ESI) was
operated in negative mode with enhanced resolution to achieve total
baseline separation of isotopic peaks. The capillary, skimmer 1,
and trap drive voltages were 3500, -22.1, and 37.7 V, respectively.
Ion charge control was on with a target of 30 000. The 350 °C
nitrogen dry gas flow rate was 12 L/min and the nebulization gas
pressure was 60 psi. Each point of the total ion current (TIC)
chromatogram consisted of an average of 8 scans over a mass range
of m/z 50-350. The mass spectra used for quantitation consisted
of an average of three to five points of the extracted ion
chromatogram (EIC) beginning at the apex of the peak. These points
were chosen to have the best signal-to-noise ratio and resolution.
Automatic generation of the mass list, intensities, and areas was
used except for the M + 2 isotope of the control sample spectra,
which was integrated manually. The M + 4 isotopic peaks were
not discernible above the baseline noise.
Calculations. Extensive descriptions of calculation methods
applied to 1a and 4a have been published.10 The same procedures
were followed for 1b-f and 4b-f utilizing Spartan 04 for
Macintosh Version 1.0.1 and Spartan Version 5.25 Geometries were
optimized at the HF/6-31G* level. Frequency analyses were
performed at this level to verify that all geometries corresponded
to true stationary points. These geometries were used to obtain
energies at the perturbative Becke-Perdew density functional level
pBP/DN*//HF/6-31G*.26 Calculations were also carried out at the
BP/6-31G*//HF/6-31G*26 level, which is implemented in Spartan
04 and at the B3LYP/6-31G*//HF/6-31G* level. Optimized HF/
6-31G* geometries and energies at all levels calculated are presented
in the Supporting Information.
Acknowledgment. The authors thank the donors of the
Petroleum Research Fund for support of this research (Grant
No. 43176-AC4). The 500 MHz NMR spectrometer and the
LC/MS were provided by grants to MU by the Hayes Investment
Fund of the Ohio Board of Regents.
Kinetics and Product Analysis. Detailed procedures for the
preparation of solutions and monitoring kinetics by UV spectro-
scopy or HPLC are provided elsewhere.8,9 Stock solutions of most
compounds were prepared at ca. 0.01 M in CH3CN to obtain initial
concentrations of 5 × 10-5 M in the reaction solutions after injection
of 15 µL of the stock solution into 3 mL of the aqueous reaction
solution. The sulfonamides 2b and 2c precipitated under these
conditions, so 0.002 M solutions of these compounds in CH3CN
were prepared to obtain 1 × 10-5 M concentrations in the reaction
medium. All reactions followed by UV spectroscopy were moni-
tored at a minimum of two wavelengths, and rate constants obtained
Supporting Information Available: Characterization of 2c-
e, 2e′, 2f′, 4b-f, 5b-f, and 6b, synthesis and characterization of
3b and 3c, optimized geometries (HF/6-31G*) for 1b-f and 4b-
f, comparison of selected HF/6-31G* bond lengths in 1a-f, and
13C NMR spectra of 2c-e, 2e′, 2f′, 4b-f, 5b-f, and 6b. This
material is available free of charge via the Internet at http://
pubs.acs.org.
JO060198R
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J. Am. Chem. Soc. 1993, 115, 9453-9460.
(25) Wavefunction, Inc.; 18401 Van Karman Ave., Suite 370, Irvine,
CA, 92612.
(26) Becke, A. D. Phys. ReV. A 1988, 38, 3098-3100. Perdew, J. P.
Phys. ReV. B 1986, 33, 8822-8824.
(22) Ou, S. H.; Percec, V.; Mann, J. A.; Lando, J. B.; Zhou, L.; Singer,
K. D. Macromolecules 1993, 26, 7263-7273.
(23) Gutsche, C. D.; No, K. H. J. Org. Chem. 1982, 47, 2708-2712.
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