Lifetimes of Imidinium Ions in Aqueous Solution
J. Am. Chem. Soc., Vol. 119, No. 31, 1997 7279
Synthetic Methods. Toluene and ethers were dried over sodium
wire and stored under nitrogen. The haloformamidines used in this
study were prepared in the following general manner from the
corresponding aniline:
δH(400 MHz; CDCl3) 7.9 (1H, d, J ) 7 Hz), 7.85 (1H, s), 7.4 (1H, t,
J ) 8 Hz), 7.3 (1H, d, J ) 7 Hz), 3.75 (4H, t, J ) 3 Hz), 3.55 (4H, t,
J ) 3 Hz); m/z 254 (100%, MH+), 234 (2%, MH - F), 224 (25%, MH
- CH2O), 181 (43%, M - C4H6O), 88.1 (40%, C4H10NO)(Found:
MH+, 254.0948. C11H13FN3O3 requires MH, 254.0941). N,N-(3-
Oxapentane-1,5-diyl)-N′-(4-nitrophenyl)fluoroformamidine, 8-F: yellow
solid; δH(400 MHz; CDCl3) 8.14 (2H, d, J ) 9 Hz), 7.08 (2H, d, J )
9 Hz), 3.78 (2H, t, J ) 4.5 Hz), 3.55 (2H, t, J ) 4.5 Hz); m/z 254
(100%, MH+), 234 (1%, M - CH2OCH2) and 209 (1%, M -
F)(Found: MH+, 254.0940. C11H13FN3O3 requires MH, 254.0941).
N-(Butane-1,5-diyl)-N′-phenylfluoroformamidine, 9-F: white solid; δH-
(400 MHz; CDCl3) 7.27-7.22 (3H, m), 6.98 (2H, m), 3.43 (4H, s),
1.63 (6H, s). N,N-(3-Azapentane-1,5-diyl)-N′-phenyl-N′′-methylfluo-
roformamidine, 10-F: white solid; δH(400 MHz; CDCl3) δ 7.4-7.2
(2H, m), 7.1-6.9 (3H, m), 3.5 (4H, t, J ) 3 Hz), 2.5 (4H, t, J ) 3 Hz),
2.35 (3H, s); m/z 221 (100%, MH+), 202 (70%, MH - F), 164 (15%,
M - C3H7N), 83 (20%, C5H9N), 70 (65%, C4H8N)(Found: MH+,
222.1386. C12H17FN3 requires MH, 222.1406). N-Methyl-N-methoxy-
N′-phenylfluoroformamidine, 11-F: clear oil; δH(400 MHz; CDCl3)
7.3 (2H, t, J ) 8 Hz, Ar), 7.1 (1H, t, J ) 8 Hz, Ar), 7.05 (2H, d, J )
8 Hz, Ar), 3.75 (3H, s), 3.15 (3H, s); m/z 181 (100%, MH+), 166 (10%,
M - CH3), 151 (1%, M - OCH3), 119 (7%, M - HNCH3(OCH3)), 61
(55%, HNCH3(OCH3)), 77 (2%, C6H5)(Found: MH+, 181.096. C9H12-
FN2O requires MH, 181.0777). 4-F was prepared by adding a solution
of 4-Cl in acetonitrile to an equal volume of aqueous 0.1 M potassium
fluoride and then adding 2 µL of the resulting solution to the reaction
mixture. The changes in the UV spectra upon hydrolysis of the
compounds that were used for kinetic analysis were all very similar
and were consistant with hydrolysis to the urea.
Kinetic Methods. The fluorides were stored at -20 °C for periods
of weeks without any noticable decomposition. The chlorides were
unstable after prolonged storage, as noted previously.38 Reaction
solutions at ionic strength 1.0 M, maintained with KCl, were prepared
in quartz cuvettes and equilibrated to 25 °C before the addition of ca.
5 µL of a 0.03 M stock solution of the substrate in acetonitrile or
dioxane. The products and substrates of the various reactions studied
had largely overlapping ultraviolet spectra. Most reactions exhibited
a shift in the ultraviolet spectrum to longer wavelength which enabled
a change in absorbance of typically 0.4 to be monitored at the
concentration of 5 × 10-5 M, that was generally used. Biphasic kinetics
were observed if the substrate was not completely dissolved, and these
runs were discarded. The reactions were followed with a Cary 1E UV-
visible spectrophotometer, a Perkin-Elmer Lamda 4B UV/vis spectro-
photometer, or a Milton Roy Company spectronic 1001. The buffer
concentration was g100 times the substrate concentration, so that
pseudo-first-order conditions were maintained. Standard conditions
were 25 °C at ionic strength 1.0, maintained with potassium chloride.
When thiolates were used, argon gas was bubbled through the reaction
cells prior to addition of reagents. All pH measurements were made
under the conditions of the kinetic experiments using an Orion Research
Digital pH meter with a 611 Corning semimicro combination electrode.
The pD of solutions in D2O was measured using the same electrode
that had been standardized against (protium) standard buffers and was
taken to be 0.4 above the reading of the pH meter.39 The absorbance
was measured at set intervals (more than ten points per half life) and
recorded either on a printer connected to the spectrophotometer or on
a computer. The data were analyzed with a Gateway 2000 4SX-33
computer using Sigma Plot. Reactions were generally followed for
>5 half lives and an end point was taken after >10 half lives. Rate
constants were obtained from semilogarithamic plots of (At - A∞)
against time. These were linear for more than five half-lives, and, where
duplicated, the rate constants were generally within 5%.
Formanilides. The aniline was refluxed overnight in formic acid
(88% v/v), and the hot solution was filtered and allowed to cool to
room temperature. Formic acid was removed by distillation under
reduced pressure, and the crude product was either recrystallized from
aqueous ethanol to give the formanilide (>90%) or used without further
purification in the next step.
Arylcarbonimidoyl Dichlorides. These were prepared following
a modification of the protocol of Hegarty.37 The formanilide (usually
about 3-5 g), 1 equiv of sulfuryl chloride, and thionyl chloride (ca.
20 mL) in a two-necked round-bottom flask fitted with a reflux
condensor were stirred overnight at room temperature. Less soluble
formanilides were warmed until they dissolved, and the solution was
stirred overnight at room temperature. The solvent was removed under
reduced pressure with a rotary evaporator to give the imidoyl dichloride
as a crude oil, which was distilled (Kugelrohr, pressure < 0.1 mmHg)
to give the dichloride as a viscous clear oil, which occasionally solidified
on storage at -20 °C. The yields were generally ca. 70%. Electron-
donating groups on the aromatic ring reduce the yields significantly
and produce more polymeric material, as has been noted previously.38
N,N-Dialkyl-N′-arylchloroformamidines. These were generally
prepared following a modification of the protocol of Hegarty.37 Two
equivalents of the amine (0.1 M in toluene) were added to a solution
of the dichloride in anhydrous toluene at 0 °C. The solution was stirred
at room temperature for 10 min and then filtered. The solvent was
removed, and the residue was distilled (Kugelrohr, pressure < 0.1
mmHg) to give the purified imidoyl chloride (>70%) as an oil that
solidified on storage.
N-Methyl-N-methoxy-N′-arylchloroformamidine. To a solution
of the dichloride in anhydrous toluene was added 1 equiv of N-methyl-
N-methoxyamine hydrochloride and 2 equiv of triethylamine (0.1 M
in toluene) at 0 °C. The product was isolated as above to give the
imidoyl chloride as a yellow solid. N-Methyl-N-methoxy-N′-(4-
nitrophenyl)chloroformamidine 12-Cl: yellow oil; δH(400 MHz;
CDCl3) 8.21 (2H, d, J ) 9 Hz, Ar), 7.00 (2H, d, J ) 9 Hz, Ar), 3.81
(3H, s), 3.30 (3H, s).
N,N-Dialkyl-N′-arylfluoroformamidines. The N,N-dialkyl-N′-aryl-
chloroformamidines were added to a saturated solution of potassium
fluoride in anhydrous trifluoroethanol and stirred for several hours. The
solvent was removed, and the residue was dissolved in chloroform and
chromatographed rapidly (SiO2, hexane-ethyl acetate, 50/50 v/v). The
isolated products were distilled (Kugelrohr, pressure < 0.1 mmHg) to
give the following N,N-dialkyl-N′-arylfluoroformamidines with >90%
yield, as solids that were scraped off the inside of the receiving flask:
N,N-(3-Oxapentane-1,5-diyl)-N′-phenylfluoroformamidine, 1-F: white
solid; m/z 209 (100%, MH+), 189 (5%, M - F) and 77 (4%,
C6H5)(Found: MH+, 209.1093. C11H14FN2O requires MH, 209.1090).
N,N-(3-Oxapentane-1,5-diyl)-N′-(4-fluorophenyl)fluoroformamidine,
2-F: white solid; m/z 225 (100%, MH+), 181 (30%, MH - CH2OCH2)
and 137 (40%, M - C4H9NO)(Found: MH+, 225.0825. C11H13FN2O
requires MH, 225.0839). N,N-(3-Oxapentane-1,5-diyl)-N′-(4-chlo-
rophenyl)fluoroformamidine, 3-F: white solid; δH(400 MHz; CDCl3)
7.27 (2H, m), 7.18 (2H, m), 3.75 (4H, m), 3.50 (4H, m); m/z 243 (100%,
MH+), 223 (3%, M - F)(Found: MH+, 243.0690. C11H13ClFN2O
requires MH, 243.0700). N,N-(3-Oxapentane-1,5-diyl)-N′-(3-cyanophe-
nyl)fluoroformamidine, 5-F: white solid; δH(400 MHz; CDCl3) 7.32
(2H, m), 7.27 (2H, m), 3.78 (4H, t, J ) 3 Hz), 3.50 (4H, t, J ) 3 Hz);
m/z 234 (100%, MH+), 88.1 (95%, C7H4 or C4H10NO)(Found: MH+,
234.1047. C12H13FN3O requires MH, 234.1043). N,N-(3-Oxapentane-
1,5-diyl)-N′-(4-cyanophenyl)fluoroformamidine, 6-F: white solid; δH-
(400 MHz; CDCl3) 7.55 (2H, d, J ) 6 Hz), 7.05 (2H, d, J ) 6 Hz),
3.77 (4H, t, J ) 3 Hz), 3.52 (4H, t, J ) 3 Hz); m/z 232 (100%, MH+),
144 (80%, M - C4H9NO), 88.1 (100%, C4H10NO)(Found: MH+,
232.0902. C12H13FNO requires MH, 232.0886). N,N-(3-Oxapentane-
1,5-diyl)-N′-(3-nitrophenyl)fluoroformamidine, 7-F: yellow solid;
Rate constant ratios knuc/kX for the reactions of nucleophiles with
the haloformamidines were determined from a plot of ksolv/(ksolv - kobs
)
against [nuc], obtained in the presence of a constant concentration of
a common halide anion, X-, according to eq 2 which is obtained simply
by rearrangement of eq 1. Values of kX/ks and ksolv were determined
by common ion inhibition in the absence of the nucleophile using eq
3.40
(37) Hegarty, A. F.; Cronin, J. D.; Scott, F. L. J. Chem. Soc., Perkin
Trans. 2 1975, 429.
(38) Ku¨hle, E. Angew. Chem., Int. Ed. Engl. 1962, 1, 647.
(39) Glasoe, P. K.; Long, F. A. J. Phys. Chem. 1960, 64, 188.
(40) See Royer R. E.; Daub, G. H.; Vander Jagt, D. L. J. Org. Chem.
1979, 44, 3196, for a similar approach.